Genome-Wide CRISPR-Cas9 Screens Expose Genetic Vulnerabilities and Mechanisms of Temozolomide Sensitivity in Glioblastoma Stem Cells

Glioblastoma therapies have remained elusive due to limitations in understanding mechanisms of growth and survival of the tumorigenic population. Using CRISPR-Cas9 approaches in patient-derived GBM stem cells (GSCs) to interrogate function of the coding genome, we identify actionable pathways respon...

Full description

Saved in:
Bibliographic Details
Published inCell reports (Cambridge) Vol. 27; no. 3; pp. 971 - 986.e9
Main Authors MacLeod, Graham, Bozek, Danielle A., Rajakulendran, Nishani, Monteiro, Vernon, Ahmadi, Moloud, Steinhart, Zachary, Kushida, Michelle M., Yu, Helen, Coutinho, Fiona J., Cavalli, Florence M.G., Restall, Ian, Hao, Xiaoguang, Hart, Traver, Luchman, H. Artee, Weiss, Samuel, Dirks, Peter B., Angers, Stephane
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 16.04.2019
Elsevier
Subjects
Online AccessGet full text
ISSN2211-1247
2211-1247
DOI10.1016/j.celrep.2019.03.047

Cover

Loading…
Abstract Glioblastoma therapies have remained elusive due to limitations in understanding mechanisms of growth and survival of the tumorigenic population. Using CRISPR-Cas9 approaches in patient-derived GBM stem cells (GSCs) to interrogate function of the coding genome, we identify actionable pathways responsible for growth, which reveal the gene-essential circuitry of GBM stemness and proliferation. In particular, we characterize members of the SOX transcription factor family, SOCS3, USP8, and DOT1L, and protein ufmylation as important for GSC growth. Additionally, we reveal mechanisms of temozolomide resistance that could lead to combination strategies. By reaching beyond static genome analysis of bulk tumors, with a genome-wide functional approach, we reveal genetic dependencies within a broad range of biological processes to provide increased understanding of GBM growth and treatment resistance. [Display omitted] •Genome-wide CRISPR-Cas9 screens in patient-derived glioblastoma stem cells•Identification of regulators of stemness governing glioblastoma stem cell growth•Multiple stress response pathways are genetic vulnerabilities in glioblastoma•Identification of modulators of sensitivity to standard of care chemotherapy MacLeod et al. describe genome-wide CRISPR-Cas9 screens identifying genetic vulnerabilities across a panel of patient-derived glioblastoma stem cell cultures. Regulators of stemness (SOX2, SOX9, DOT1L, and SOCS3) and stress response (ufmylation and ERAD pathways) govern the growth of glioblastoma stem cells. Chemogenomic screens using temozolomide identify modulators of sensitivity to chemotherapy.
AbstractList Glioblastoma therapies have remained elusive due to limitations in understanding mechanisms of growth and survival of the tumorigenic population. Using CRISPR-Cas9 approaches in patient-derived GBM stem cells (GSCs) to interrogate function of the coding genome, we identify actionable pathways responsible for growth, which reveal the gene-essential circuitry of GBM stemness and proliferation. In particular, we characterize members of the SOX transcription factor family, SOCS3, USP8, and DOT1L, and protein ufmylation as important for GSC growth. Additionally, we reveal mechanisms of temozolomide resistance that could lead to combination strategies. By reaching beyond static genome analysis of bulk tumors, with a genome-wide functional approach, we reveal genetic dependencies within a broad range of biological processes to provide increased understanding of GBM growth and treatment resistance.Glioblastoma therapies have remained elusive due to limitations in understanding mechanisms of growth and survival of the tumorigenic population. Using CRISPR-Cas9 approaches in patient-derived GBM stem cells (GSCs) to interrogate function of the coding genome, we identify actionable pathways responsible for growth, which reveal the gene-essential circuitry of GBM stemness and proliferation. In particular, we characterize members of the SOX transcription factor family, SOCS3, USP8, and DOT1L, and protein ufmylation as important for GSC growth. Additionally, we reveal mechanisms of temozolomide resistance that could lead to combination strategies. By reaching beyond static genome analysis of bulk tumors, with a genome-wide functional approach, we reveal genetic dependencies within a broad range of biological processes to provide increased understanding of GBM growth and treatment resistance.
Glioblastoma therapies have remained elusive due to limitations in understanding mechanisms of growth and survival of the tumorigenic population. Using CRISPR-Cas9 approaches in patient-derived GBM stem cells (GSCs) to interrogate function of the coding genome, we identify actionable pathways responsible for growth, which reveal the gene-essential circuitry of GBM stemness and proliferation. In particular, we characterize members of the SOX transcription factor family, SOCS3, USP8, and DOT1L, and protein ufmylation as important for GSC growth. Additionally, we reveal mechanisms of temozolomide resistance that could lead to combination strategies. By reaching beyond static genome analysis of bulk tumors, with a genome-wide functional approach, we reveal genetic dependencies within a broad range of biological processes to provide increased understanding of GBM growth and treatment resistance.
Glioblastoma therapies have remained elusive due to limitations in understanding mechanisms of growth and survival of the tumorigenic population. Using CRISPR-Cas9 approaches in patient-derived GBM stem cells (GSCs) to interrogate function of the coding genome, we identify actionable pathways responsible for growth, which reveal the gene-essential circuitry of GBM stemness and proliferation. In particular, we characterize members of the SOX transcription factor family, SOCS3, USP8, and DOT1L, and protein ufmylation as important for GSC growth. Additionally, we reveal mechanisms of temozolomide resistance that could lead to combination strategies. By reaching beyond static genome analysis of bulk tumors, with a genome-wide functional approach, we reveal genetic dependencies within a broad range of biological processes to provide increased understanding of GBM growth and treatment resistance. [Display omitted] •Genome-wide CRISPR-Cas9 screens in patient-derived glioblastoma stem cells•Identification of regulators of stemness governing glioblastoma stem cell growth•Multiple stress response pathways are genetic vulnerabilities in glioblastoma•Identification of modulators of sensitivity to standard of care chemotherapy MacLeod et al. describe genome-wide CRISPR-Cas9 screens identifying genetic vulnerabilities across a panel of patient-derived glioblastoma stem cell cultures. Regulators of stemness (SOX2, SOX9, DOT1L, and SOCS3) and stress response (ufmylation and ERAD pathways) govern the growth of glioblastoma stem cells. Chemogenomic screens using temozolomide identify modulators of sensitivity to chemotherapy.
Glioblastoma therapies have remained elusive due to limitations in understanding mechanisms of growth and survival of the tumorigenic population. Using CRISPR-Cas9 approaches in patient-derived GBM stem cells (GSCs) to interrogate function of the coding genome, we identify actionable pathways responsible for growth, which reveal the gene-essential circuitry of GBM stemness and proliferation. In particular, we characterize members of the SOX transcription factor family, SOCS3, USP8, and DOT1L, and protein ufmylation as important for GSC growth. Additionally, we reveal mechanisms of temozolomide resistance that could lead to combination strategies. By reaching beyond static genome analysis of bulk tumors, with a genome-wide functional approach, we reveal genetic dependencies within a broad range of biological processes to provide increased understanding of GBM growth and treatment resistance. : MacLeod et al. describe genome-wide CRISPR-Cas9 screens identifying genetic vulnerabilities across a panel of patient-derived glioblastoma stem cell cultures. Regulators of stemness (SOX2, SOX9, DOT1L, and SOCS3) and stress response (ufmylation and ERAD pathways) govern the growth of glioblastoma stem cells. Chemogenomic screens using temozolomide identify modulators of sensitivity to chemotherapy. Keywords: glioblastoma, glioblastoma stem cells, CRISPR-Cas9, fitness genes, functional genomics
Author Cavalli, Florence M.G.
Weiss, Samuel
Dirks, Peter B.
Luchman, H. Artee
Coutinho, Fiona J.
Steinhart, Zachary
Ahmadi, Moloud
Restall, Ian
Yu, Helen
Hao, Xiaoguang
Angers, Stephane
Bozek, Danielle A.
Monteiro, Vernon
Hart, Traver
MacLeod, Graham
Rajakulendran, Nishani
Kushida, Michelle M.
Author_xml – sequence: 1
  givenname: Graham
  surname: MacLeod
  fullname: MacLeod, Graham
  organization: Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada
– sequence: 2
  givenname: Danielle A.
  surname: Bozek
  fullname: Bozek, Danielle A.
  organization: Hotchkiss Brain Institute, Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
– sequence: 3
  givenname: Nishani
  surname: Rajakulendran
  fullname: Rajakulendran, Nishani
  organization: Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada
– sequence: 4
  givenname: Vernon
  surname: Monteiro
  fullname: Monteiro, Vernon
  organization: Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada
– sequence: 5
  givenname: Moloud
  surname: Ahmadi
  fullname: Ahmadi, Moloud
  organization: Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada
– sequence: 6
  givenname: Zachary
  surname: Steinhart
  fullname: Steinhart, Zachary
  organization: Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada
– sequence: 7
  givenname: Michelle M.
  surname: Kushida
  fullname: Kushida, Michelle M.
  organization: Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada
– sequence: 8
  givenname: Helen
  surname: Yu
  fullname: Yu, Helen
  organization: Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada
– sequence: 9
  givenname: Fiona J.
  surname: Coutinho
  fullname: Coutinho, Fiona J.
  organization: Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada
– sequence: 10
  givenname: Florence M.G.
  surname: Cavalli
  fullname: Cavalli, Florence M.G.
  organization: Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada
– sequence: 11
  givenname: Ian
  surname: Restall
  fullname: Restall, Ian
  organization: Hotchkiss Brain Institute, Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
– sequence: 12
  givenname: Xiaoguang
  surname: Hao
  fullname: Hao, Xiaoguang
  organization: Hotchkiss Brain Institute, Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
– sequence: 13
  givenname: Traver
  surname: Hart
  fullname: Hart, Traver
  organization: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
– sequence: 14
  givenname: H. Artee
  surname: Luchman
  fullname: Luchman, H. Artee
  organization: Hotchkiss Brain Institute, Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
– sequence: 15
  givenname: Samuel
  surname: Weiss
  fullname: Weiss, Samuel
  organization: Hotchkiss Brain Institute, Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
– sequence: 16
  givenname: Peter B.
  surname: Dirks
  fullname: Dirks, Peter B.
  email: peter.dirks@sickkids.ca
  organization: Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada
– sequence: 17
  givenname: Stephane
  orcidid: 0000-0001-7241-9044
  surname: Angers
  fullname: Angers, Stephane
  email: stephane.angers@utoronto.ca
  organization: Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada
BackLink https://www.ncbi.nlm.nih.gov/pubmed/30995489$$D View this record in MEDLINE/PubMed
BookMark eNqFkUFvFCEYhiemxtbaf2AMRy8zAsPMLB5MzKSum9RoulWPBJhvlA0DW2Ab69kfLuO0xnhQLhDyvA_hex8XR847KIqnBFcEk_bFrtJgA-wrigmvcF1h1j0oTiglpCSUdUd_nI-Lsxh3OK8WE8LZo-K4xpw3bMVPih9rcH6C8rMZAPWXm-2Hy7KXkaOtDgAuovNvex8BZQyS0ejTwToIUhlrkoGIpBvQO9BfpTNxisiP6Aom_91bP83GbVZk8MakW2QcWlvjlZUx-UmibYIJ9WBtfFI8HKWNcHa3nxYf35xf9W_Li_frTf_6otSsY6mUA8e4U0A7DdC1jabDAAQzoM3Y0m4kI6m5pIRTVaummdmBMrrSiq543fD6tNgs3sHLndgHM8lwK7w04teFD1-EDPmXFgRuCBlb3nHZAtOylStKR6y5UkpLwiC7ni-uffDXB4hJTCbmUqx04A9RzOOvacdWdUaf3aEHNcHw--H7FjLwcgF08DEGGIU2SSbjXQrSWEGwmFsXO7G0LubWBa5Fbj2H2V_he_9_Yq-WGOSB3xgIImoDTsNgAuiUJ2L-LfgJftPIew
CitedBy_id crossref_primary_10_1158_0008_5472_CAN_23_4024
crossref_primary_10_1038_s41467_023_40776_y
crossref_primary_10_1002_jnr_24850
crossref_primary_10_1038_s41568_024_00763_x
crossref_primary_10_1080_14728222_2020_1820986
crossref_primary_10_1038_s41571_024_00966_z
crossref_primary_10_1016_j_slasd_2022_09_002
crossref_primary_10_1016_j_pharmthera_2021_107922
crossref_primary_10_3390_ijms25147979
crossref_primary_10_1007_s10555_023_10114_1
crossref_primary_10_2174_1566523222666220831161225
crossref_primary_10_1016_j_cell_2020_05_040
crossref_primary_10_1038_s41598_019_50160_w
crossref_primary_10_1158_1078_0432_CCR_21_1299
crossref_primary_10_1038_s41598_021_88613_w
crossref_primary_10_1038_s41598_021_82137_z
crossref_primary_10_1124_pharmrev_120_000053
crossref_primary_10_3390_ijms22084011
crossref_primary_10_3390_life13040905
crossref_primary_10_1002_cjp2_134
crossref_primary_10_3389_fonc_2022_1075559
crossref_primary_10_1002_1878_0261_13020
crossref_primary_10_1007_s12033_023_00699_x
crossref_primary_10_1172_jci_insight_149232
crossref_primary_10_1038_s41467_023_38044_0
crossref_primary_10_1093_neuonc_noac271
crossref_primary_10_1038_s41591_024_03138_9
crossref_primary_10_1016_j_jconrel_2024_09_019
crossref_primary_10_1254_fpj_20072
crossref_primary_10_1042_EBC20220009
crossref_primary_10_1186_s12974_022_02399_w
crossref_primary_10_1042_ETLS20210222
crossref_primary_10_3389_fimmu_2024_1454823
crossref_primary_10_3389_fonc_2022_790976
crossref_primary_10_1016_j_mcp_2024_102004
crossref_primary_10_1016_j_yexcr_2022_113063
crossref_primary_10_1038_s42003_021_01929_1
crossref_primary_10_1038_s41417_023_00608_z
crossref_primary_10_1016_j_ebiom_2023_104752
crossref_primary_10_1002_1878_0261_13355
crossref_primary_10_3390_cancers15245790
crossref_primary_10_1007_s00401_024_02831_w
crossref_primary_10_1126_sciadv_ade5321
crossref_primary_10_1016_j_celrep_2021_108903
crossref_primary_10_3390_cancers12061518
crossref_primary_10_1038_s41417_023_00664_5
crossref_primary_10_1186_s13046_024_03027_6
crossref_primary_10_3389_fmolb_2020_620677
crossref_primary_10_3390_ijms23094511
crossref_primary_10_3390_cancers15020396
crossref_primary_10_3389_fgene_2022_839884
crossref_primary_10_1186_s13073_019_0665_3
crossref_primary_10_1016_j_prp_2024_155727
crossref_primary_10_1073_pnas_2202015119
crossref_primary_10_1080_07357907_2021_1952595
crossref_primary_10_1101_gad_329508_119
crossref_primary_10_3389_fonc_2020_574011
crossref_primary_10_1016_j_neuron_2023_04_021
crossref_primary_10_3390_ijms24054467
crossref_primary_10_3390_biom12050703
crossref_primary_10_1038_s41467_021_21204_5
crossref_primary_10_1038_s41401_024_01456_9
crossref_primary_10_2139_ssrn_4066204
crossref_primary_10_1158_2159_8290_CD_20_1848
crossref_primary_10_1038_s41416_020_01136_5
crossref_primary_10_3390_ijms23052509
crossref_primary_10_3390_ijms25147868
crossref_primary_10_1007_s11055_024_01651_5
crossref_primary_10_1093_noajnl_vdac156
crossref_primary_10_3390_ijms25115702
crossref_primary_10_1016_j_compbiomed_2023_107750
crossref_primary_10_1093_nar_gkae1122
crossref_primary_10_1172_jci_insight_158077
crossref_primary_10_3390_ijms21175962
crossref_primary_10_1038_s41467_023_38919_2
crossref_primary_10_3390_cancers11070921
crossref_primary_10_1038_s41598_024_68626_x
crossref_primary_10_1016_j_gene_2023_147476
crossref_primary_10_1016_j_devcel_2021_12_007
crossref_primary_10_1158_1535_7163_MCT_20_0319
crossref_primary_10_3390_biology13121008
crossref_primary_10_1007_s12033_020_00289_1
crossref_primary_10_1158_0008_5472_CAN_24_3304
crossref_primary_10_3389_fcell_2024_1436563
crossref_primary_10_1158_2159_8290_CD_20_0331
crossref_primary_10_3390_cancers14092211
crossref_primary_10_3390_cancers13051013
crossref_primary_10_3390_cells10051225
crossref_primary_10_1038_s43018_020_00154_9
crossref_primary_10_1038_s44319_023_00017_1
crossref_primary_10_1038_s41467_022_31408_y
crossref_primary_10_3390_ijms21144910
crossref_primary_10_3390_cells9122573
crossref_primary_10_1016_j_cell_2020_04_047
crossref_primary_10_1007_s12033_022_00550_9
crossref_primary_10_3389_fgene_2022_864612
crossref_primary_10_1038_s41467_020_17549_y
crossref_primary_10_3390_cells10092342
crossref_primary_10_3390_cancers13071494
crossref_primary_10_1016_j_semcancer_2023_02_003
crossref_primary_10_1016_j_plantsci_2025_112435
crossref_primary_10_1126_sciadv_adj7706
crossref_primary_10_1016_j_lfs_2024_123132
crossref_primary_10_1016_j_cellsig_2025_111657
crossref_primary_10_31857_S0044467724010037
crossref_primary_10_7554_eLife_64090
crossref_primary_10_1002_1878_0261_13735
crossref_primary_10_2174_1570180819666220121145332
crossref_primary_10_3390_cancers13030381
crossref_primary_10_3390_cancers14194942
crossref_primary_10_3390_ijms222413213
crossref_primary_10_1089_omi_2023_0124
crossref_primary_10_1093_neuonc_noae062
crossref_primary_10_3390_ijms22073493
crossref_primary_10_1038_s41392_023_01666_3
crossref_primary_10_1016_j_tibs_2023_10_004
crossref_primary_10_1016_j_ccell_2020_10_015
crossref_primary_10_1016_j_biopha_2021_112585
crossref_primary_10_1038_s41596_023_00835_6
crossref_primary_10_1158_1541_7786_MCR_22_0418
crossref_primary_10_1038_s41467_020_16718_3
crossref_primary_10_1038_s41588_021_00926_8
crossref_primary_10_1093_neuonc_noaa259
crossref_primary_10_1126_sciadv_aaz4848
crossref_primary_10_1158_2767_9764_CRC_23_0144
crossref_primary_10_1038_s41388_021_01882_7
crossref_primary_10_3389_fgene_2022_904060
crossref_primary_10_3389_fonc_2024_1383062
crossref_primary_10_1186_s12967_022_03284_z
crossref_primary_10_3390_cancers15061897
crossref_primary_10_3390_cancers14092304
crossref_primary_10_1042_BST20190527
crossref_primary_10_3390_cancers15133458
crossref_primary_10_1093_neuonc_noae072
crossref_primary_10_1093_neuonc_noad252
crossref_primary_10_1186_s13578_021_00575_8
crossref_primary_10_3390_cancers14153743
crossref_primary_10_1038_s43018_024_00748_7
crossref_primary_10_3389_fphar_2023_1284610
crossref_primary_10_3389_fmicb_2024_1362487
crossref_primary_10_1371_journal_pone_0257473
crossref_primary_10_1186_s12885_021_07967_6
crossref_primary_10_3390_biom14030335
Cites_doi 10.1126/science.1254257
10.1126/science.1246981
10.1111/j.1471-4159.2006.03890.x
10.1038/nature25975
10.1016/j.molcel.2017.12.020
10.1093/nar/gkw937
10.1093/nar/gkw419
10.1016/j.semcancer.2015.02.003
10.1091/mbc.e05-06-0560
10.1056/NEJMoa043330
10.1016/j.cell.2015.11.015
10.1186/s12915-014-0094-0
10.1038/ng.3967
10.1007/s00280-015-2929-y
10.1016/j.cell.2014.02.030
10.1073/pnas.1320611111
10.1038/nmeth.2019
10.1093/neuonc/now247
10.1038/srep00516
10.1534/g3.117.041277
10.1038/nmeth.1541
10.1158/1078-0432.CCR-06-2303
10.1016/j.ccr.2006.03.030
10.7554/eLife.17290
10.1038/nprot.2007.202
10.1038/nature07385
10.1126/science.aac7041
10.1038/s41586-018-0389-3
10.1038/ng.3984
10.1038/nature10860
10.1016/j.stem.2009.03.014
10.1158/0008-5472.CAN-06-0127
10.1126/science.1230161
10.1016/j.jim.2009.06.008
10.1038/nature23000
10.3389/fncel.2017.00023
10.1371/journal.pone.0048587
10.1038/nbt1010-1015
10.1007/s11060-016-2156-3
10.1186/s13059-014-0554-4
10.1093/nar/gkw199
10.1016/j.ccell.2015.10.005
10.1038/sj.emboj.7600692
10.1158/2159-8290.CD-18-0389
10.1056/NEJMra0708126
10.1038/nature23666
10.1038/nature13228
10.1016/j.bcp.2016.04.008
10.1371/journal.pone.0006529
10.1158/2159-8290.CD-16-0154
10.1093/nar/gku936
10.1038/ng.3590
10.1002/ijc.23805
10.1038/nbt.3519
10.1074/mcp.M114.045658
10.1007/s00109-006-0153-2
10.1016/j.cell.2013.09.034
10.1016/j.molcel.2015.09.002
10.1186/1471-2105-10-48
10.1016/j.molcel.2015.07.010
10.1021/acschembio.7b00020
10.1016/j.ccell.2016.05.002
10.1038/43206
10.1126/science.1164382
10.1038/nature11287
10.1186/s12859-016-1015-8
10.1038/onc.2011.634
10.1038/nm.4219
10.1101/gr.1239303
10.1016/j.ccr.2006.05.013
10.1073/pnas.1001613107
10.1016/j.molcel.2012.05.047
10.1007/978-1-61779-276-2_12
10.1016/j.celrep.2015.11.021
10.1038/s41586-018-0291-z
10.1186/s13059-014-0550-8
10.1126/science.1247005
ContentType Journal Article
Copyright 2019 The Authors
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
Copyright_xml – notice: 2019 The Authors
– notice: Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
DBID 6I.
AAFTH
AAYXX
CITATION
NPM
7X8
DOA
DOI 10.1016/j.celrep.2019.03.047
DatabaseName ScienceDirect Open Access Titles
Elsevier:ScienceDirect:Open Access
CrossRef
PubMed
MEDLINE - Academic
DOAJ Directory of Open Access Journals
DatabaseTitle CrossRef
PubMed
MEDLINE - Academic
DatabaseTitleList MEDLINE - Academic
PubMed


Database_xml – sequence: 1
  dbid: DOA
  name: DOAJ Directory of Open Access Journals
  url: https://www.doaj.org/
  sourceTypes: Open Website
– sequence: 2
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Biology
EISSN 2211-1247
EndPage 986.e9
ExternalDocumentID oai_doaj_org_article_0511f6979a6e4ca6a822f0c9bbbca14e
30995489
10_1016_j_celrep_2019_03_047
S2211124719303638
Genre Research Support, U.S. Gov't, Non-P.H.S
Research Support, Non-U.S. Gov't
Journal Article
Research Support, N.I.H., Extramural
GrantInformation_xml – fundername: CIHR
– fundername: NCI NIH HHS
  grantid: P30 CA016672
GroupedDBID 0R~
0SF
4.4
457
53G
5VS
6I.
AACTN
AAEDT
AAEDW
AAFTH
AAIKJ
AAKRW
AALRI
AAUCE
AAXUO
ABMAC
ABMWF
ACGFO
ACGFS
ADBBV
ADEZE
AENEX
AEXQZ
AFTJW
AGHFR
AITUG
ALKID
ALMA_UNASSIGNED_HOLDINGS
AMRAJ
BAWUL
BCNDV
DIK
EBS
EJD
FCP
FDB
FRP
GROUPED_DOAJ
GX1
IXB
KQ8
M41
M48
NCXOZ
O-L
O9-
OK1
RCE
RIG
ROL
SSZ
AAMRU
AAYWO
AAYXX
ACVFH
ADCNI
ADVLN
AEUPX
AFPUW
AIGII
AKBMS
AKRWK
AKYEP
APXCP
CITATION
HZ~
IPNFZ
NPM
7X8
ID FETCH-LOGICAL-c474t-ad9007be27cee765c2dde104e25f627f1f139a2192b3b55007bd2428cb2893593
IEDL.DBID M48
ISSN 2211-1247
IngestDate Wed Aug 27 01:29:42 EDT 2025
Fri Sep 05 05:16:34 EDT 2025
Thu Jan 02 23:00:34 EST 2025
Tue Jul 01 02:59:01 EDT 2025
Thu Apr 24 22:58:02 EDT 2025
Wed May 17 00:03:04 EDT 2023
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 3
Keywords functional genomics
glioblastoma
fitness genes
glioblastoma stem cells
CRISPR-Cas9
Language English
License This is an open access article under the CC BY-NC-ND license.
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c474t-ad9007be27cee765c2dde104e25f627f1f139a2192b3b55007bd2428cb2893593
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ORCID 0000-0001-7241-9044
OpenAccessLink http://journals.scholarsportal.info/openUrl.xqy?doi=10.1016/j.celrep.2019.03.047
PMID 30995489
PQID 2211327483
PQPubID 23479
ParticipantIDs doaj_primary_oai_doaj_org_article_0511f6979a6e4ca6a822f0c9bbbca14e
proquest_miscellaneous_2211327483
pubmed_primary_30995489
crossref_citationtrail_10_1016_j_celrep_2019_03_047
crossref_primary_10_1016_j_celrep_2019_03_047
elsevier_sciencedirect_doi_10_1016_j_celrep_2019_03_047
ProviderPackageCode CITATION
AAYXX
PublicationCentury 2000
PublicationDate 2019-04-16
PublicationDateYYYYMMDD 2019-04-16
PublicationDate_xml – month: 04
  year: 2019
  text: 2019-04-16
  day: 16
PublicationDecade 2010
PublicationPlace United States
PublicationPlace_xml – name: United States
PublicationTitle Cell reports (Cambridge)
PublicationTitleAlternate Cell Rep
PublicationYear 2019
Publisher Elsevier Inc
Elsevier
Publisher_xml – name: Elsevier Inc
– name: Elsevier
References Zhang, Zhang, Wu, Lei, Li (bib75) 2012; 7
Gallo, Coutinho, Vanner, Gayden, Mack, Murison, Remke, Li, Takayama, Desai (bib20) 2015; 28
Waters, Smith, Olhava, Duncan, Burton, O’Neill, Rodrigue, Pollock, Moyer, Chesworth (bib70) 2016; 77
Wang, Edelmann (bib66) 2006; 9
Pollard, Yoshikawa, Clarke, Danovi, Stricker, Russell, Bayani, Head, Lee, Bernstein (bib49) 2009; 4
Roberts, Miyamoto, Huffman, Bateman, Ives, Akopian, Heslin, Contreras, Rape, Skibola, Nomura (bib52) 2017; 12
Toledo, Ding, Hoellerbauer, Davis, Basom, Girard, Lee, Corrin, Hart, Bolouri (bib63) 2015; 13
Love, Huber, Anders (bib34) 2014; 15
Martini, Pallini, Luongo, Cenci, Lucantoni, Larocca (bib36) 2008; 123
Mizuno, Iura, Mukai, Yoshimori, Kitamura, Komada (bib42) 2005; 16
Aguirre, Meyers, Weir, Vazquez, Zhang, Ben-David, Cook, Ha, Harrington, Doshi (bib1) 2016; 6
Li, Xu, Xiao, Cong, Love, Zhang, Irizarry, Liu, Brown, Liu (bib31) 2014; 15
Merico, Isserlin, Bader (bib38) 2011; 781
Nishimura, Ishiai, Horikawa, Fukagawa, Takata, Takisawa, Kanemaki (bib43) 2012; 47
Youn, Dunham, Hong, Knight, Bashkurov, Chen, Bagci, Rathod, MacLeod, Eng (bib74) 2018; 69
Liu, Hon, Villa, Turner, Ikegami, Yang, Ye, Li, Kuan, Lee (bib33) 2015; 60
Parsons, Jones, Zhang, Lin, Leary, Angenendt, Mankoo, Carter, Siu, Gallia (bib45) 2008; 321
Wang, Cazzato, Ladewig, Frattini, Rosenbloom, Zairis, Abate, Liu, Elliott, Shin (bib69) 2016; 48
Matsuda, Sato, Okada, Shibuya, Seino, Suzuki, Watanabe, Narita, Shibui, Kayama, Kitanaka (bib37) 2012; 2
Katan-Khaykovich, Struhl (bib26) 2005; 24
Schindelin, Arganda-Carreras, Frise, Kaynig, Longair, Pietzsch, Preibisch, Rueden, Saalfeld, Schmid (bib54) 2012; 9
Zimmermann, Murina, Reijns, Agathanggelou, Challis, Tarnauskaitė, Muir, Fluteau, Aregger, McEwan (bib77) 2018; 559
Podobinska, Szablowska-Gadomska, Augustyniak, Sandvig, Sandvig, Buzanska (bib48) 2017; 11
Yoon, Kim, Kim, Lim, Choi, An, Hwang, Kang, Suh, Park, Lee (bib73) 2012; 31
Szklarczyk, Morris, Cook, Kuhn, Wyder, Simonovic, Santos, Doncheva, Roth, Bork (bib62) 2017; 45
Dolma, Selvadurai, Lan, Lee, Kushida, Voisin, Whetstone, So, Aviv, Park (bib17) 2016; 29
Suvà, Rheinbay, Gillespie, Patel, Wakimoto, Rabkin, Riggi, Chi, Cahill, Nahed (bib61) 2014; 157
Steinhart, Pavlovic, Chandrashekhar, Hart, Wang, Zhang, Robitaille, Brown, Jaksani, Overmeer (bib59) 2017; 23
Peñaranda Fajardo, Meijer, Kruyt (bib47) 2016; 118
Brennan, Verhaak, McKenna, Campos, Noushmehr, Salama, Zheng, Chakravarty, Sanborn, Berman (bib6) 2013; 155
Choi, Larsen, Lin, Breitkreutz, Mellacheruvu, Fermin, Qin, Tyers, Gingras, Nesvizhskii (bib13) 2011; 8
Hart, Chandrashekhar, Aregger, Steinhart, Brown, MacLeod, Mis, Zimmermann, Fradet-Turcotte, Sun (bib22) 2015; 163
Hunter, Smith, Cahill, Stephens, Stevens, Teague, Greenman, Edkins, Bignell, Davies (bib25) 2006; 66
Ben-David, Ha, Tseng, Greenwald, Oh, Shih, McFarland, Wong, Boehm, Beroukhim, Golub (bib3) 2017; 49
Traver, Coulombe, Peiffer, Hutchins, Kitzmann, Latreille, Méchali (bib64) 2015; 59
Raizer, Chandler, Ferrarese, Grimm, Levy, Muro, Rosenow, Helenowski, Rademaker, Paton, Bredel (bib50) 2016; 129
Coyaud, Mis, Laurent, Dunham, Couzens, Robitaille, Gingras, Angers, Raught (bib14) 2015; 14
Ernst, Avvakumov, Tong, Fan, Zhao, Alberts, Persaud, Walker, Neculai, Neculai (bib19) 2013; 339
Lu, Ward, Kapoor, Rohle, Turcan, Abdel-Wahab, Edwards, Khanin, Figueroa, Melnick (bib35) 2012; 483
Reimand, Arak, Adler, Kolberg, Reisberg, Peterson, Vilo (bib51) 2016; 44
Hart, Tong, Chan, Van Leeuwen, Seetharaman, Aregger, Chandrashekhar, Hustedt, Seth, Noonan (bib23) 2017; 7
Lee, Lee, Kahng, Kim, Park, Yoon, Um, Kim, Lee, Park (bib30) 2018; 560
Sorrells, Paredes, Cebrian-Silla, Sandoval, Qi, Kelley, James, Mayer, Chang, Auguste (bib57) 2018; 555
Hu, Smyth (bib24) 2009; 347
Eden, Navon, Steinfeld, Lipson, Yakhini (bib18) 2009; 10
Cao, Hata, Zhu, Ma, Tanaka, Hanakawa, Hashimoto, Niinobe, Yoshikawa, Sakanaka (bib10) 2006; 98
Shannon, Markiel, Ozier, Baliga, Wang, Ramage, Amin, Schwikowski, Ideker (bib53) 2003; 13
Liu, Zhang, Larsen, Stark, Breitkreutz, Lin, Breitkreutz, Ding, Colwill, Pasculescu (bib32) 2010; 28
Shalem, Sanjana, Hartenian, Shi, Scott, Mikkelson, Heckl, Ebert, Root, Doench, Zhang (bib55) 2014; 343
(bib9) 2008; 455
Starr, Willson, Viney, Murray, Rayner, Jenkins, Gonda, Alexander, Metcalf, Nicola, Hilton (bib58) 1997; 387
Wen, Kesari (bib71) 2008; 359
Chen, Li, Yu, McKay, Burns, Kernie, Parada (bib12) 2012; 488
Wang, Birsoy, Hughes, Krupczak, Post, Wei, Lander, Sabatini (bib68) 2015; 350
Hart, Moffat (bib21) 2016; 17
Meyers, Bryan, McFarland, Weir, Sizemore, Xu, Dharia, Montgomery, Cowley, Pantel (bib40) 2017; 49
Kim, Bhattacharya, Qi (bib27) 2015; 33
Patel, Tirosh, Trombetta, Shalek, Gillespie, Wakimoto, Cahill, Nahed, Curry, Martuza (bib46) 2014; 344
Wang, Wei, Sabatini, Lander (bib67) 2014; 343
Chen, Taniguchi, D’Andrea (bib11) 2007; 85
Lan, Jörg, Cavalli, Richards, Nguyen, Vanner, Guilhamon, Lee, Kushida, Pellacani (bib28) 2017; 549
Babicki, Arndt, Marcu, Liang, Grant, Maciejewski, Wishart (bib2) 2016; 44
DeJesus, Moretti, McAllister, Wang, Bergman, Liu, Frias, Alford, Reece-Hoyes, Lindeman (bib15) 2016; 5
Zhou, Miki, Eeva, Fike, Seligson, Yang, Yoshimura, Teitell, Jamieson, Cacalano (bib76) 2007; 13
Campeau, Ruhl, Rodier, Smith, Rahmberg, Fuss, Campisi, Yaswen, Cooper, Kaufman (bib8) 2009; 4
van Galen, Kreso, Mbong, Kent, Fitzmaurice, Chambers, Xie, Laurenti, Hermans, Eppert (bib65) 2014; 510
Wiedemeyer, Dunn, Quayle, Zhang, Chheda, Dunn, Zhuang, Rosenbluh, Chen, Xiao (bib72) 2010; 107
Stupp, Mason, van den Bent, Weller, Fisher, Taphoorn, Belanger, Brandes, Marosi, Bogdahn (bib60) 2005; 352
Bray, Pimentel, Melsted, Pachter (bib5) 2016; 34
Miller, Liau, Wallace, Morton, Xie, Dixit, Factor, Kim, Morrow, Wu (bib41) 2017; 547
Brinkman, Chen, Amendola, van Steensel (bib7) 2014; 42
Lee, Kotliarova, Kotliarov, Li, Su, Donin, Pastorino, Purow, Christopher, Zhang (bib29) 2006; 9
Oser, Fonseca, Chakraborty, Brough, Spektor, Jennings, Flaifel, Novak, Gulati, Buss (bib44) 2019; 9
Shechter, Dormann, Allis, Hake (bib56) 2007; 2
Deshaies (bib16) 2014; 12
Bowman, Wang, Carro, Verhaak, Squatrito (bib4) 2017; 19
Meyer, Reimand, Lan, Head, Zhu, Kushida, Bayani, Pressey, Lionel, Clarke (bib39) 2015; 112
Wang (10.1016/j.celrep.2019.03.047_bib66) 2006; 9
Meyer (10.1016/j.celrep.2019.03.047_bib39) 2015; 112
Youn (10.1016/j.celrep.2019.03.047_bib74) 2018; 69
Chen (10.1016/j.celrep.2019.03.047_bib12) 2012; 488
Hart (10.1016/j.celrep.2019.03.047_bib23) 2017; 7
Stupp (10.1016/j.celrep.2019.03.047_bib60) 2005; 352
Shannon (10.1016/j.celrep.2019.03.047_bib53) 2003; 13
Lee (10.1016/j.celrep.2019.03.047_bib29) 2006; 9
Merico (10.1016/j.celrep.2019.03.047_bib38) 2011; 781
Wiedemeyer (10.1016/j.celrep.2019.03.047_bib72) 2010; 107
Lee (10.1016/j.celrep.2019.03.047_bib30) 2018; 560
Li (10.1016/j.celrep.2019.03.047_bib31) 2014; 15
Campeau (10.1016/j.celrep.2019.03.047_bib8) 2009; 4
Wang (10.1016/j.celrep.2019.03.047_bib67) 2014; 343
Hart (10.1016/j.celrep.2019.03.047_bib22) 2015; 163
Shalem (10.1016/j.celrep.2019.03.047_bib55) 2014; 343
DeJesus (10.1016/j.celrep.2019.03.047_bib15) 2016; 5
Martini (10.1016/j.celrep.2019.03.047_bib36) 2008; 123
Roberts (10.1016/j.celrep.2019.03.047_bib52) 2017; 12
Love (10.1016/j.celrep.2019.03.047_bib34) 2014; 15
Wen (10.1016/j.celrep.2019.03.047_bib71) 2008; 359
Mizuno (10.1016/j.celrep.2019.03.047_bib42) 2005; 16
Kim (10.1016/j.celrep.2019.03.047_bib27) 2015; 33
Peñaranda Fajardo (10.1016/j.celrep.2019.03.047_bib47) 2016; 118
Coyaud (10.1016/j.celrep.2019.03.047_bib14) 2015; 14
Lu (10.1016/j.celrep.2019.03.047_bib35) 2012; 483
Brinkman (10.1016/j.celrep.2019.03.047_bib7) 2014; 42
Szklarczyk (10.1016/j.celrep.2019.03.047_bib62) 2017; 45
Shechter (10.1016/j.celrep.2019.03.047_bib56) 2007; 2
Aguirre (10.1016/j.celrep.2019.03.047_bib1) 2016; 6
Nishimura (10.1016/j.celrep.2019.03.047_bib43) 2012; 47
Choi (10.1016/j.celrep.2019.03.047_bib13) 2011; 8
Lan (10.1016/j.celrep.2019.03.047_bib28) 2017; 549
Pollard (10.1016/j.celrep.2019.03.047_bib49) 2009; 4
Deshaies (10.1016/j.celrep.2019.03.047_bib16) 2014; 12
Steinhart (10.1016/j.celrep.2019.03.047_bib59) 2017; 23
van Galen (10.1016/j.celrep.2019.03.047_bib65) 2014; 510
Matsuda (10.1016/j.celrep.2019.03.047_bib37) 2012; 2
Zhang (10.1016/j.celrep.2019.03.047_bib75) 2012; 7
Oser (10.1016/j.celrep.2019.03.047_bib44) 2019; 9
Bowman (10.1016/j.celrep.2019.03.047_bib4) 2017; 19
Yoon (10.1016/j.celrep.2019.03.047_bib73) 2012; 31
Toledo (10.1016/j.celrep.2019.03.047_bib63) 2015; 13
Starr (10.1016/j.celrep.2019.03.047_bib58) 1997; 387
Katan-Khaykovich (10.1016/j.celrep.2019.03.047_bib26) 2005; 24
Traver (10.1016/j.celrep.2019.03.047_bib64) 2015; 59
Wang (10.1016/j.celrep.2019.03.047_bib68) 2015; 350
Babicki (10.1016/j.celrep.2019.03.047_bib2) 2016; 44
Sorrells (10.1016/j.celrep.2019.03.047_bib57) 2018; 555
Eden (10.1016/j.celrep.2019.03.047_bib18) 2009; 10
Waters (10.1016/j.celrep.2019.03.047_bib70) 2016; 77
Raizer (10.1016/j.celrep.2019.03.047_bib50) 2016; 129
Schindelin (10.1016/j.celrep.2019.03.047_bib54) 2012; 9
Suvà (10.1016/j.celrep.2019.03.047_bib61) 2014; 157
Hunter (10.1016/j.celrep.2019.03.047_bib25) 2006; 66
Zimmermann (10.1016/j.celrep.2019.03.047_bib77) 2018; 559
Parsons (10.1016/j.celrep.2019.03.047_bib45) 2008; 321
(10.1016/j.celrep.2019.03.047_bib9) 2008; 455
Hart (10.1016/j.celrep.2019.03.047_bib21) 2016; 17
Gallo (10.1016/j.celrep.2019.03.047_bib20) 2015; 28
Meyers (10.1016/j.celrep.2019.03.047_bib40) 2017; 49
Cao (10.1016/j.celrep.2019.03.047_bib10) 2006; 98
Ernst (10.1016/j.celrep.2019.03.047_bib19) 2013; 339
Podobinska (10.1016/j.celrep.2019.03.047_bib48) 2017; 11
Dolma (10.1016/j.celrep.2019.03.047_bib17) 2016; 29
Hu (10.1016/j.celrep.2019.03.047_bib24) 2009; 347
Liu (10.1016/j.celrep.2019.03.047_bib33) 2015; 60
Brennan (10.1016/j.celrep.2019.03.047_bib6) 2013; 155
Reimand (10.1016/j.celrep.2019.03.047_bib51) 2016; 44
Miller (10.1016/j.celrep.2019.03.047_bib41) 2017; 547
Chen (10.1016/j.celrep.2019.03.047_bib11) 2007; 85
Liu (10.1016/j.celrep.2019.03.047_bib32) 2010; 28
Ben-David (10.1016/j.celrep.2019.03.047_bib3) 2017; 49
Wang (10.1016/j.celrep.2019.03.047_bib69) 2016; 48
Patel (10.1016/j.celrep.2019.03.047_bib46) 2014; 344
Bray (10.1016/j.celrep.2019.03.047_bib5) 2016; 34
Zhou (10.1016/j.celrep.2019.03.047_bib76) 2007; 13
References_xml – volume: 510
  start-page: 268
  year: 2014
  end-page: 272
  ident: bib65
  article-title: The unfolded protein response governs integrity of the haematopoietic stem-cell pool during stress
  publication-title: Nature
– volume: 31
  start-page: 4655
  year: 2012
  end-page: 4666
  ident: bib73
  article-title: c-Jun N-terminal kinase has a pivotal role in the maintenance of self-renewal and tumorigenicity in glioma stem-like cells
  publication-title: Oncogene
– volume: 49
  start-page: 1567
  year: 2017
  end-page: 1575
  ident: bib3
  article-title: Patient-derived xenografts undergo mouse-specific tumor evolution
  publication-title: Nat. Genet.
– volume: 66
  start-page: 3987
  year: 2006
  end-page: 3991
  ident: bib25
  article-title: A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy
  publication-title: Cancer Res.
– volume: 129
  start-page: 139
  year: 2016
  end-page: 146
  ident: bib50
  article-title: A phase II trial evaluating the effects and intra-tumoral penetration of bortezomib in patients with recurrent malignant gliomas
  publication-title: J. Neurooncol.
– volume: 155
  start-page: 462
  year: 2013
  end-page: 477
  ident: bib6
  article-title: The somatic genomic landscape of glioblastoma
  publication-title: Cell
– volume: 7
  start-page: e48587
  year: 2012
  ident: bib75
  article-title: Transcriptional regulation of the Ufm1 conjugation system in response to disturbance of the endoplasmic reticulum homeostasis and inhibition of vesicle trafficking
  publication-title: PLoS ONE
– volume: 12
  start-page: 94
  year: 2014
  ident: bib16
  article-title: Proteotoxic crisis, the ubiquitin-proteasome system, and cancer therapy
  publication-title: BMC Biol.
– volume: 4
  start-page: e6529
  year: 2009
  ident: bib8
  article-title: A versatile viral system for expression and depletion of proteins in mammalian cells
  publication-title: PLoS ONE
– volume: 15
  start-page: 550
  year: 2014
  ident: bib34
  article-title: Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
  publication-title: Genome Biol.
– volume: 157
  start-page: 580
  year: 2014
  end-page: 594
  ident: bib61
  article-title: Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells
  publication-title: Cell
– volume: 321
  start-page: 1807
  year: 2008
  end-page: 1812
  ident: bib45
  article-title: An integrated genomic analysis of human glioblastoma multiforme
  publication-title: Science
– volume: 549
  start-page: 227
  year: 2017
  end-page: 232
  ident: bib28
  article-title: Fate mapping of human glioblastoma reveals an invariant stem cell hierarchy
  publication-title: Nature
– volume: 98
  start-page: 459
  year: 2006
  end-page: 470
  ident: bib10
  article-title: Overexpression of SOCS3 inhibits astrogliogenesis and promotes maintenance of neural stem cells
  publication-title: J. Neurochem.
– volume: 17
  start-page: 164
  year: 2016
  ident: bib21
  article-title: BAGEL: a computational framework for identifying essential genes from pooled library screens
  publication-title: BMC Bioinformatics
– volume: 2
  start-page: 1445
  year: 2007
  end-page: 1457
  ident: bib56
  article-title: Extraction, purification and analysis of histones
  publication-title: Nat. Protoc.
– volume: 350
  start-page: 1096
  year: 2015
  end-page: 1101
  ident: bib68
  article-title: Identification and characterization of essential genes in the human genome
  publication-title: Science
– volume: 9
  start-page: 417
  year: 2006
  end-page: 418
  ident: bib66
  article-title: Mismatch repair proteins as sensors of alkylation DNA damage
  publication-title: Cancer Cell
– volume: 555
  start-page: 377
  year: 2018
  end-page: 381
  ident: bib57
  article-title: Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults
  publication-title: Nature
– volume: 347
  start-page: 70
  year: 2009
  end-page: 78
  ident: bib24
  article-title: ELDA: extreme limiting dilution analysis for comparing depleted and enriched populations in stem cell and other assays
  publication-title: J. Immunol. Methods
– volume: 24
  start-page: 2138
  year: 2005
  end-page: 2149
  ident: bib26
  article-title: Heterochromatin formation involves changes in histone modifications over multiple cell generations
  publication-title: EMBO J.
– volume: 16
  start-page: 5163
  year: 2005
  end-page: 5174
  ident: bib42
  article-title: Regulation of epidermal growth factor receptor down-regulation by UBPY-mediated deubiquitination at endosomes
  publication-title: Mol. Biol. Cell
– volume: 387
  start-page: 917
  year: 1997
  end-page: 921
  ident: bib58
  article-title: A family of cytokine-inducible inhibitors of signalling
  publication-title: Nature
– volume: 483
  start-page: 474
  year: 2012
  end-page: 478
  ident: bib35
  article-title: IDH mutation impairs histone demethylation and results in a block to cell differentiation
  publication-title: Nature
– volume: 2
  start-page: 516
  year: 2012
  ident: bib37
  article-title: Targeting JNK for therapeutic depletion of stem-like glioblastoma cells
  publication-title: Sci. Rep.
– volume: 112
  start-page: 851
  year: 2015
  end-page: 856
  ident: bib39
  article-title: Single cell-derived clonal analysis of human glioblastoma links functional and genomic heterogeneity
  publication-title: Proc. Natl. Acad. Sci. USA
– volume: 339
  start-page: 590
  year: 2013
  end-page: 595
  ident: bib19
  article-title: A strategy for modulation of enzymes in the ubiquitin system
  publication-title: Science
– volume: 33
  start-page: 25
  year: 2015
  end-page: 33
  ident: bib27
  article-title: Endoplasmic reticulum quality control in cancer: friend or foe
  publication-title: Semin. Cancer Biol.
– volume: 13
  start-page: 2498
  year: 2003
  end-page: 2504
  ident: bib53
  article-title: Cytoscape: a software environment for integrated models of biomolecular interaction networks
  publication-title: Genome Res.
– volume: 23
  start-page: 60
  year: 2017
  end-page: 68
  ident: bib59
  article-title: Genome-wide CRISPR screens reveal a Wnt-FZD5 signaling circuit as a druggable vulnerability of RNF43-mutant pancreatic tumors
  publication-title: Nat. Med.
– volume: 19
  start-page: 139
  year: 2017
  end-page: 141
  ident: bib4
  article-title: GlioVis data portal for visualization and analysis of brain tumor expression datasets
  publication-title: Neuro-oncol.
– volume: 9
  start-page: 230
  year: 2019
  end-page: 247
  ident: bib44
  article-title: Cells lacking the RB1 tumor suppressor gene are hyperdependent on Aurora B kinase for survival
  publication-title: Cancer Discov.
– volume: 5
  start-page: e17290
  year: 2016
  ident: bib15
  article-title: Functional CRISPR screening identifies the ufmylation pathway as a regulator of SQSTM1/p62
  publication-title: eLife
– volume: 107
  start-page: 11501
  year: 2010
  end-page: 11506
  ident: bib72
  article-title: Pattern of retinoblastoma pathway inactivation dictates response to CDK4/6 inhibition in GBM
  publication-title: Proc. Natl. Acad. Sci. USA
– volume: 45
  start-page: D362
  year: 2017
  end-page: D368
  ident: bib62
  article-title: The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible
  publication-title: Nucleic Acids Res.
– volume: 6
  start-page: 914
  year: 2016
  end-page: 929
  ident: bib1
  article-title: Genomic copy number dictates a gene-independent cell response to CRISPR/Cas9 targeting
  publication-title: Cancer Discov.
– volume: 29
  start-page: 859
  year: 2016
  end-page: 873
  ident: bib17
  article-title: Inhibition of dopamine receptor D4 impedes autophagic flux, proliferation, and survival of glioblastoma stem cells
  publication-title: Cancer Cell
– volume: 28
  start-page: 1015
  year: 2010
  end-page: 1017
  ident: bib32
  article-title: ProHits: integrated software for mass spectrometry-based interaction proteomics
  publication-title: Nat. Biotechnol.
– volume: 163
  start-page: 1515
  year: 2015
  end-page: 1526
  ident: bib22
  article-title: High-resolution CRISPR screens reveal fitness genes and genotype-specific cancer liabilities
  publication-title: Cell
– volume: 59
  start-page: 831
  year: 2015
  end-page: 839
  ident: bib64
  article-title: MCM9 is required for mammalian DNA mismatch repair
  publication-title: Mol. Cell
– volume: 28
  start-page: 715
  year: 2015
  end-page: 729
  ident: bib20
  article-title: MLL5 orchestrates a cancer self-renewal state by repressing the histone variant H3.3 and globally reorganizing chromatin
  publication-title: Cancer Cell
– volume: 69
  start-page: 517
  year: 2018
  end-page: 532.e11
  ident: bib74
  article-title: High-density proximity mapping reveals the subcellular organization of mRNA-associated granules and bodies
  publication-title: Mol. Cell
– volume: 12
  start-page: 899
  year: 2017
  end-page: 904
  ident: bib52
  article-title: Chemoproteomic screening of covalent ligands reveals UBA5 as a novel pancreatic cancer target
  publication-title: ACS Chem. Biol.
– volume: 343
  start-page: 80
  year: 2014
  end-page: 84
  ident: bib67
  article-title: Genetic screens in human cells using the CRISPR-Cas9 system
  publication-title: Science
– volume: 9
  start-page: 676
  year: 2012
  end-page: 682
  ident: bib54
  article-title: Fiji: an open-source platform for biological-image analysis
  publication-title: Nat. Methods
– volume: 49
  start-page: 1779
  year: 2017
  end-page: 1784
  ident: bib40
  article-title: Computational correction of copy number effect improves specificity of CRISPR-Cas9 essentiality screens in cancer cells
  publication-title: Nat. Genet.
– volume: 359
  start-page: 492
  year: 2008
  end-page: 507
  ident: bib71
  article-title: Malignant gliomas in adults
  publication-title: N. Engl. J. Med.
– volume: 48
  start-page: 768
  year: 2016
  end-page: 776
  ident: bib69
  article-title: Clonal evolution of glioblastoma under therapy
  publication-title: Nat. Genet.
– volume: 85
  start-page: 497
  year: 2007
  end-page: 509
  ident: bib11
  article-title: The Fanconi anemia (FA) pathway confers glioma resistance to DNA alkylating agents
  publication-title: J. Mol. Med. (Berl.)
– volume: 34
  start-page: 525
  year: 2016
  end-page: 527
  ident: bib5
  article-title: Near-optimal probabilistic RNA-seq quantification
  publication-title: Nat. Biotechnol.
– volume: 15
  start-page: 554
  year: 2014
  ident: bib31
  article-title: MAGeCK enables robust identification of essential genes from genome-scale CRISPR/Cas9 knockout screens
  publication-title: Genome Biol.
– volume: 4
  start-page: 568
  year: 2009
  end-page: 580
  ident: bib49
  article-title: Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens
  publication-title: Cell Stem Cell
– volume: 7
  start-page: 2719
  year: 2017
  end-page: 2727
  ident: bib23
  article-title: Evaluation and design of genome-wide CRISPR/SpCas9 knockout screens
  publication-title: G3 (Bethesda)
– volume: 455
  start-page: 1061
  year: 2008
  end-page: 1068
  ident: bib9
  article-title: Comprehensive genomic characterization defines human glioblastoma genes and core pathways
  publication-title: Nature
– volume: 13
  start-page: 2344
  year: 2007
  end-page: 2353
  ident: bib76
  article-title: Reciprocal regulation of SOCS1 and SOCS3 enhances resistance to ionizing radiation in glioblastoma multiforme
  publication-title: Clin. Cancer Res.
– volume: 781
  start-page: 257
  year: 2011
  end-page: 277
  ident: bib38
  article-title: Visualizing gene-set enrichment results using the Cytoscape plug-in enrichment map
  publication-title: Methods Mol. Biol.
– volume: 343
  start-page: 84
  year: 2014
  end-page: 87
  ident: bib55
  article-title: Genome-scale CRISPR-Cas9 knockout screening in human cells
  publication-title: Science
– volume: 559
  start-page: 285
  year: 2018
  end-page: 289
  ident: bib77
  article-title: CRISPR screens identify genomic ribonucleotides as a source of PARP-trapping lesions
  publication-title: Nature
– volume: 11
  start-page: 23
  year: 2017
  ident: bib48
  article-title: Epigenetic modulation of stem cells in neurodevelopment: the role of methylation and acetylation
  publication-title: Front. Cell. Neurosci.
– volume: 560
  start-page: 243
  year: 2018
  end-page: 247
  ident: bib30
  article-title: Human glioblastoma arises from subventricular zone cells with low-level driver mutations
  publication-title: Nature
– volume: 344
  start-page: 1396
  year: 2014
  end-page: 1401
  ident: bib46
  article-title: Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma
  publication-title: Science
– volume: 44
  start-page: W83
  year: 2016
  end-page: W89
  ident: bib51
  article-title: g:Profiler-a web server for functional interpretation of gene lists (2016 update)
  publication-title: Nucleic Acids Res.
– volume: 47
  start-page: 511
  year: 2012
  end-page: 522
  ident: bib43
  article-title: Mcm8 and Mcm9 form a complex that functions in homologous recombination repair induced by DNA interstrand crosslinks
  publication-title: Mol. Cell
– volume: 44
  start-page: W147
  year: 2016
  end-page: W153
  ident: bib2
  article-title: Heatmapper: web-enabled heat mapping for all
  publication-title: Nucleic Acids Res.
– volume: 10
  start-page: 48
  year: 2009
  ident: bib18
  article-title: GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists
  publication-title: BMC Bioinformatics
– volume: 13
  start-page: 2425
  year: 2015
  end-page: 2439
  ident: bib63
  article-title: Genome-wide CRISPR-Cas9 screens reveal loss of redundancy between PKMYT1 and WEE1 in glioblastoma stem-like cells
  publication-title: Cell Rep.
– volume: 42
  start-page: e168
  year: 2014
  ident: bib7
  article-title: Easy quantitative assessment of genome editing by sequence trace decomposition
  publication-title: Nucleic Acids Res.
– volume: 9
  start-page: 391
  year: 2006
  end-page: 403
  ident: bib29
  article-title: Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines
  publication-title: Cancer Cell
– volume: 352
  start-page: 987
  year: 2005
  end-page: 996
  ident: bib60
  article-title: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma
  publication-title: N. Engl. J. Med.
– volume: 547
  start-page: 355
  year: 2017
  end-page: 359
  ident: bib41
  article-title: Transcription elongation factors represent in vivo cancer dependencies in glioblastoma
  publication-title: Nature
– volume: 118
  start-page: 1
  year: 2016
  end-page: 8
  ident: bib47
  article-title: The endoplasmic reticulum stress/unfolded protein response in gliomagenesis, tumor progression and as a therapeutic target in glioblastoma
  publication-title: Biochem. Pharmacol.
– volume: 8
  start-page: 70
  year: 2011
  end-page: 73
  ident: bib13
  article-title: SAINT: probabilistic scoring of affinity purification-mass spectrometry data
  publication-title: Nat. Methods
– volume: 123
  start-page: 2955
  year: 2008
  end-page: 2960
  ident: bib36
  article-title: Prognostic relevance of SOCS3 hypermethylation in patients with glioblastoma multiforme
  publication-title: Int. J. Cancer
– volume: 14
  start-page: 1781
  year: 2015
  end-page: 1795
  ident: bib14
  article-title: BioID-based identification of Skp Cullin F-box (SCF)β-TrCP1/2 E3 ligase substrates
  publication-title: Mol. Cell. Proteomics
– volume: 488
  start-page: 522
  year: 2012
  end-page: 526
  ident: bib12
  article-title: A restricted cell population propagates glioblastoma growth after chemotherapy
  publication-title: Nature
– volume: 77
  start-page: 43
  year: 2016
  end-page: 62
  ident: bib70
  article-title: Metabolism and disposition of the DOT1L inhibitor, pinometostat (EPZ-5676), in rat, dog and human
  publication-title: Cancer Chemother. Pharmacol.
– volume: 60
  start-page: 307
  year: 2015
  end-page: 318
  ident: bib33
  article-title: EGFR mutation promotes glioblastoma through epigenome and transcription factor network remodeling
  publication-title: Mol. Cell
– volume: 344
  start-page: 1396
  year: 2014
  ident: 10.1016/j.celrep.2019.03.047_bib46
  article-title: Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma
  publication-title: Science
  doi: 10.1126/science.1254257
– volume: 343
  start-page: 80
  year: 2014
  ident: 10.1016/j.celrep.2019.03.047_bib67
  article-title: Genetic screens in human cells using the CRISPR-Cas9 system
  publication-title: Science
  doi: 10.1126/science.1246981
– volume: 98
  start-page: 459
  year: 2006
  ident: 10.1016/j.celrep.2019.03.047_bib10
  article-title: Overexpression of SOCS3 inhibits astrogliogenesis and promotes maintenance of neural stem cells
  publication-title: J. Neurochem.
  doi: 10.1111/j.1471-4159.2006.03890.x
– volume: 555
  start-page: 377
  year: 2018
  ident: 10.1016/j.celrep.2019.03.047_bib57
  article-title: Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults
  publication-title: Nature
  doi: 10.1038/nature25975
– volume: 69
  start-page: 517
  year: 2018
  ident: 10.1016/j.celrep.2019.03.047_bib74
  article-title: High-density proximity mapping reveals the subcellular organization of mRNA-associated granules and bodies
  publication-title: Mol. Cell
  doi: 10.1016/j.molcel.2017.12.020
– volume: 45
  start-page: D362
  issue: D1
  year: 2017
  ident: 10.1016/j.celrep.2019.03.047_bib62
  article-title: The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible
  publication-title: Nucleic Acids Res.
  doi: 10.1093/nar/gkw937
– volume: 44
  start-page: W147
  issue: W1
  year: 2016
  ident: 10.1016/j.celrep.2019.03.047_bib2
  article-title: Heatmapper: web-enabled heat mapping for all
  publication-title: Nucleic Acids Res.
  doi: 10.1093/nar/gkw419
– volume: 33
  start-page: 25
  year: 2015
  ident: 10.1016/j.celrep.2019.03.047_bib27
  article-title: Endoplasmic reticulum quality control in cancer: friend or foe
  publication-title: Semin. Cancer Biol.
  doi: 10.1016/j.semcancer.2015.02.003
– volume: 16
  start-page: 5163
  year: 2005
  ident: 10.1016/j.celrep.2019.03.047_bib42
  article-title: Regulation of epidermal growth factor receptor down-regulation by UBPY-mediated deubiquitination at endosomes
  publication-title: Mol. Biol. Cell
  doi: 10.1091/mbc.e05-06-0560
– volume: 352
  start-page: 987
  year: 2005
  ident: 10.1016/j.celrep.2019.03.047_bib60
  article-title: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMoa043330
– volume: 163
  start-page: 1515
  year: 2015
  ident: 10.1016/j.celrep.2019.03.047_bib22
  article-title: High-resolution CRISPR screens reveal fitness genes and genotype-specific cancer liabilities
  publication-title: Cell
  doi: 10.1016/j.cell.2015.11.015
– volume: 12
  start-page: 94
  year: 2014
  ident: 10.1016/j.celrep.2019.03.047_bib16
  article-title: Proteotoxic crisis, the ubiquitin-proteasome system, and cancer therapy
  publication-title: BMC Biol.
  doi: 10.1186/s12915-014-0094-0
– volume: 49
  start-page: 1567
  year: 2017
  ident: 10.1016/j.celrep.2019.03.047_bib3
  article-title: Patient-derived xenografts undergo mouse-specific tumor evolution
  publication-title: Nat. Genet.
  doi: 10.1038/ng.3967
– volume: 77
  start-page: 43
  year: 2016
  ident: 10.1016/j.celrep.2019.03.047_bib70
  article-title: Metabolism and disposition of the DOT1L inhibitor, pinometostat (EPZ-5676), in rat, dog and human
  publication-title: Cancer Chemother. Pharmacol.
  doi: 10.1007/s00280-015-2929-y
– volume: 157
  start-page: 580
  year: 2014
  ident: 10.1016/j.celrep.2019.03.047_bib61
  article-title: Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells
  publication-title: Cell
  doi: 10.1016/j.cell.2014.02.030
– volume: 112
  start-page: 851
  year: 2015
  ident: 10.1016/j.celrep.2019.03.047_bib39
  article-title: Single cell-derived clonal analysis of human glioblastoma links functional and genomic heterogeneity
  publication-title: Proc. Natl. Acad. Sci. USA
  doi: 10.1073/pnas.1320611111
– volume: 9
  start-page: 676
  year: 2012
  ident: 10.1016/j.celrep.2019.03.047_bib54
  article-title: Fiji: an open-source platform for biological-image analysis
  publication-title: Nat. Methods
  doi: 10.1038/nmeth.2019
– volume: 19
  start-page: 139
  year: 2017
  ident: 10.1016/j.celrep.2019.03.047_bib4
  article-title: GlioVis data portal for visualization and analysis of brain tumor expression datasets
  publication-title: Neuro-oncol.
  doi: 10.1093/neuonc/now247
– volume: 2
  start-page: 516
  year: 2012
  ident: 10.1016/j.celrep.2019.03.047_bib37
  article-title: Targeting JNK for therapeutic depletion of stem-like glioblastoma cells
  publication-title: Sci. Rep.
  doi: 10.1038/srep00516
– volume: 7
  start-page: 2719
  year: 2017
  ident: 10.1016/j.celrep.2019.03.047_bib23
  article-title: Evaluation and design of genome-wide CRISPR/SpCas9 knockout screens
  publication-title: G3 (Bethesda)
  doi: 10.1534/g3.117.041277
– volume: 8
  start-page: 70
  year: 2011
  ident: 10.1016/j.celrep.2019.03.047_bib13
  article-title: SAINT: probabilistic scoring of affinity purification-mass spectrometry data
  publication-title: Nat. Methods
  doi: 10.1038/nmeth.1541
– volume: 13
  start-page: 2344
  year: 2007
  ident: 10.1016/j.celrep.2019.03.047_bib76
  article-title: Reciprocal regulation of SOCS1 and SOCS3 enhances resistance to ionizing radiation in glioblastoma multiforme
  publication-title: Clin. Cancer Res.
  doi: 10.1158/1078-0432.CCR-06-2303
– volume: 9
  start-page: 391
  year: 2006
  ident: 10.1016/j.celrep.2019.03.047_bib29
  article-title: Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines
  publication-title: Cancer Cell
  doi: 10.1016/j.ccr.2006.03.030
– volume: 5
  start-page: e17290
  year: 2016
  ident: 10.1016/j.celrep.2019.03.047_bib15
  article-title: Functional CRISPR screening identifies the ufmylation pathway as a regulator of SQSTM1/p62
  publication-title: eLife
  doi: 10.7554/eLife.17290
– volume: 2
  start-page: 1445
  year: 2007
  ident: 10.1016/j.celrep.2019.03.047_bib56
  article-title: Extraction, purification and analysis of histones
  publication-title: Nat. Protoc.
  doi: 10.1038/nprot.2007.202
– volume: 455
  start-page: 1061
  year: 2008
  ident: 10.1016/j.celrep.2019.03.047_bib9
  article-title: Comprehensive genomic characterization defines human glioblastoma genes and core pathways
  publication-title: Nature
  doi: 10.1038/nature07385
– volume: 350
  start-page: 1096
  year: 2015
  ident: 10.1016/j.celrep.2019.03.047_bib68
  article-title: Identification and characterization of essential genes in the human genome
  publication-title: Science
  doi: 10.1126/science.aac7041
– volume: 560
  start-page: 243
  year: 2018
  ident: 10.1016/j.celrep.2019.03.047_bib30
  article-title: Human glioblastoma arises from subventricular zone cells with low-level driver mutations
  publication-title: Nature
  doi: 10.1038/s41586-018-0389-3
– volume: 49
  start-page: 1779
  year: 2017
  ident: 10.1016/j.celrep.2019.03.047_bib40
  article-title: Computational correction of copy number effect improves specificity of CRISPR-Cas9 essentiality screens in cancer cells
  publication-title: Nat. Genet.
  doi: 10.1038/ng.3984
– volume: 483
  start-page: 474
  year: 2012
  ident: 10.1016/j.celrep.2019.03.047_bib35
  article-title: IDH mutation impairs histone demethylation and results in a block to cell differentiation
  publication-title: Nature
  doi: 10.1038/nature10860
– volume: 4
  start-page: 568
  year: 2009
  ident: 10.1016/j.celrep.2019.03.047_bib49
  article-title: Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens
  publication-title: Cell Stem Cell
  doi: 10.1016/j.stem.2009.03.014
– volume: 66
  start-page: 3987
  year: 2006
  ident: 10.1016/j.celrep.2019.03.047_bib25
  article-title: A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy
  publication-title: Cancer Res.
  doi: 10.1158/0008-5472.CAN-06-0127
– volume: 339
  start-page: 590
  year: 2013
  ident: 10.1016/j.celrep.2019.03.047_bib19
  article-title: A strategy for modulation of enzymes in the ubiquitin system
  publication-title: Science
  doi: 10.1126/science.1230161
– volume: 347
  start-page: 70
  year: 2009
  ident: 10.1016/j.celrep.2019.03.047_bib24
  article-title: ELDA: extreme limiting dilution analysis for comparing depleted and enriched populations in stem cell and other assays
  publication-title: J. Immunol. Methods
  doi: 10.1016/j.jim.2009.06.008
– volume: 547
  start-page: 355
  year: 2017
  ident: 10.1016/j.celrep.2019.03.047_bib41
  article-title: Transcription elongation factors represent in vivo cancer dependencies in glioblastoma
  publication-title: Nature
  doi: 10.1038/nature23000
– volume: 11
  start-page: 23
  year: 2017
  ident: 10.1016/j.celrep.2019.03.047_bib48
  article-title: Epigenetic modulation of stem cells in neurodevelopment: the role of methylation and acetylation
  publication-title: Front. Cell. Neurosci.
  doi: 10.3389/fncel.2017.00023
– volume: 7
  start-page: e48587
  year: 2012
  ident: 10.1016/j.celrep.2019.03.047_bib75
  article-title: Transcriptional regulation of the Ufm1 conjugation system in response to disturbance of the endoplasmic reticulum homeostasis and inhibition of vesicle trafficking
  publication-title: PLoS ONE
  doi: 10.1371/journal.pone.0048587
– volume: 28
  start-page: 1015
  year: 2010
  ident: 10.1016/j.celrep.2019.03.047_bib32
  article-title: ProHits: integrated software for mass spectrometry-based interaction proteomics
  publication-title: Nat. Biotechnol.
  doi: 10.1038/nbt1010-1015
– volume: 129
  start-page: 139
  year: 2016
  ident: 10.1016/j.celrep.2019.03.047_bib50
  article-title: A phase II trial evaluating the effects and intra-tumoral penetration of bortezomib in patients with recurrent malignant gliomas
  publication-title: J. Neurooncol.
  doi: 10.1007/s11060-016-2156-3
– volume: 15
  start-page: 554
  year: 2014
  ident: 10.1016/j.celrep.2019.03.047_bib31
  article-title: MAGeCK enables robust identification of essential genes from genome-scale CRISPR/Cas9 knockout screens
  publication-title: Genome Biol.
  doi: 10.1186/s13059-014-0554-4
– volume: 44
  start-page: W83
  issue: W1
  year: 2016
  ident: 10.1016/j.celrep.2019.03.047_bib51
  article-title: g:Profiler-a web server for functional interpretation of gene lists (2016 update)
  publication-title: Nucleic Acids Res.
  doi: 10.1093/nar/gkw199
– volume: 28
  start-page: 715
  year: 2015
  ident: 10.1016/j.celrep.2019.03.047_bib20
  article-title: MLL5 orchestrates a cancer self-renewal state by repressing the histone variant H3.3 and globally reorganizing chromatin
  publication-title: Cancer Cell
  doi: 10.1016/j.ccell.2015.10.005
– volume: 24
  start-page: 2138
  year: 2005
  ident: 10.1016/j.celrep.2019.03.047_bib26
  article-title: Heterochromatin formation involves changes in histone modifications over multiple cell generations
  publication-title: EMBO J.
  doi: 10.1038/sj.emboj.7600692
– volume: 9
  start-page: 230
  year: 2019
  ident: 10.1016/j.celrep.2019.03.047_bib44
  article-title: Cells lacking the RB1 tumor suppressor gene are hyperdependent on Aurora B kinase for survival
  publication-title: Cancer Discov.
  doi: 10.1158/2159-8290.CD-18-0389
– volume: 359
  start-page: 492
  year: 2008
  ident: 10.1016/j.celrep.2019.03.047_bib71
  article-title: Malignant gliomas in adults
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMra0708126
– volume: 549
  start-page: 227
  year: 2017
  ident: 10.1016/j.celrep.2019.03.047_bib28
  article-title: Fate mapping of human glioblastoma reveals an invariant stem cell hierarchy
  publication-title: Nature
  doi: 10.1038/nature23666
– volume: 510
  start-page: 268
  year: 2014
  ident: 10.1016/j.celrep.2019.03.047_bib65
  article-title: The unfolded protein response governs integrity of the haematopoietic stem-cell pool during stress
  publication-title: Nature
  doi: 10.1038/nature13228
– volume: 118
  start-page: 1
  year: 2016
  ident: 10.1016/j.celrep.2019.03.047_bib47
  article-title: The endoplasmic reticulum stress/unfolded protein response in gliomagenesis, tumor progression and as a therapeutic target in glioblastoma
  publication-title: Biochem. Pharmacol.
  doi: 10.1016/j.bcp.2016.04.008
– volume: 4
  start-page: e6529
  year: 2009
  ident: 10.1016/j.celrep.2019.03.047_bib8
  article-title: A versatile viral system for expression and depletion of proteins in mammalian cells
  publication-title: PLoS ONE
  doi: 10.1371/journal.pone.0006529
– volume: 6
  start-page: 914
  year: 2016
  ident: 10.1016/j.celrep.2019.03.047_bib1
  article-title: Genomic copy number dictates a gene-independent cell response to CRISPR/Cas9 targeting
  publication-title: Cancer Discov.
  doi: 10.1158/2159-8290.CD-16-0154
– volume: 42
  start-page: e168
  year: 2014
  ident: 10.1016/j.celrep.2019.03.047_bib7
  article-title: Easy quantitative assessment of genome editing by sequence trace decomposition
  publication-title: Nucleic Acids Res.
  doi: 10.1093/nar/gku936
– volume: 48
  start-page: 768
  year: 2016
  ident: 10.1016/j.celrep.2019.03.047_bib69
  article-title: Clonal evolution of glioblastoma under therapy
  publication-title: Nat. Genet.
  doi: 10.1038/ng.3590
– volume: 123
  start-page: 2955
  year: 2008
  ident: 10.1016/j.celrep.2019.03.047_bib36
  article-title: Prognostic relevance of SOCS3 hypermethylation in patients with glioblastoma multiforme
  publication-title: Int. J. Cancer
  doi: 10.1002/ijc.23805
– volume: 34
  start-page: 525
  year: 2016
  ident: 10.1016/j.celrep.2019.03.047_bib5
  article-title: Near-optimal probabilistic RNA-seq quantification
  publication-title: Nat. Biotechnol.
  doi: 10.1038/nbt.3519
– volume: 14
  start-page: 1781
  year: 2015
  ident: 10.1016/j.celrep.2019.03.047_bib14
  article-title: BioID-based identification of Skp Cullin F-box (SCF)β-TrCP1/2 E3 ligase substrates
  publication-title: Mol. Cell. Proteomics
  doi: 10.1074/mcp.M114.045658
– volume: 85
  start-page: 497
  year: 2007
  ident: 10.1016/j.celrep.2019.03.047_bib11
  article-title: The Fanconi anemia (FA) pathway confers glioma resistance to DNA alkylating agents
  publication-title: J. Mol. Med. (Berl.)
  doi: 10.1007/s00109-006-0153-2
– volume: 155
  start-page: 462
  year: 2013
  ident: 10.1016/j.celrep.2019.03.047_bib6
  article-title: The somatic genomic landscape of glioblastoma
  publication-title: Cell
  doi: 10.1016/j.cell.2013.09.034
– volume: 60
  start-page: 307
  year: 2015
  ident: 10.1016/j.celrep.2019.03.047_bib33
  article-title: EGFR mutation promotes glioblastoma through epigenome and transcription factor network remodeling
  publication-title: Mol. Cell
  doi: 10.1016/j.molcel.2015.09.002
– volume: 10
  start-page: 48
  year: 2009
  ident: 10.1016/j.celrep.2019.03.047_bib18
  article-title: GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists
  publication-title: BMC Bioinformatics
  doi: 10.1186/1471-2105-10-48
– volume: 59
  start-page: 831
  year: 2015
  ident: 10.1016/j.celrep.2019.03.047_bib64
  article-title: MCM9 is required for mammalian DNA mismatch repair
  publication-title: Mol. Cell
  doi: 10.1016/j.molcel.2015.07.010
– volume: 12
  start-page: 899
  year: 2017
  ident: 10.1016/j.celrep.2019.03.047_bib52
  article-title: Chemoproteomic screening of covalent ligands reveals UBA5 as a novel pancreatic cancer target
  publication-title: ACS Chem. Biol.
  doi: 10.1021/acschembio.7b00020
– volume: 29
  start-page: 859
  year: 2016
  ident: 10.1016/j.celrep.2019.03.047_bib17
  article-title: Inhibition of dopamine receptor D4 impedes autophagic flux, proliferation, and survival of glioblastoma stem cells
  publication-title: Cancer Cell
  doi: 10.1016/j.ccell.2016.05.002
– volume: 387
  start-page: 917
  year: 1997
  ident: 10.1016/j.celrep.2019.03.047_bib58
  article-title: A family of cytokine-inducible inhibitors of signalling
  publication-title: Nature
  doi: 10.1038/43206
– volume: 321
  start-page: 1807
  year: 2008
  ident: 10.1016/j.celrep.2019.03.047_bib45
  article-title: An integrated genomic analysis of human glioblastoma multiforme
  publication-title: Science
  doi: 10.1126/science.1164382
– volume: 488
  start-page: 522
  year: 2012
  ident: 10.1016/j.celrep.2019.03.047_bib12
  article-title: A restricted cell population propagates glioblastoma growth after chemotherapy
  publication-title: Nature
  doi: 10.1038/nature11287
– volume: 17
  start-page: 164
  year: 2016
  ident: 10.1016/j.celrep.2019.03.047_bib21
  article-title: BAGEL: a computational framework for identifying essential genes from pooled library screens
  publication-title: BMC Bioinformatics
  doi: 10.1186/s12859-016-1015-8
– volume: 31
  start-page: 4655
  year: 2012
  ident: 10.1016/j.celrep.2019.03.047_bib73
  article-title: c-Jun N-terminal kinase has a pivotal role in the maintenance of self-renewal and tumorigenicity in glioma stem-like cells
  publication-title: Oncogene
  doi: 10.1038/onc.2011.634
– volume: 23
  start-page: 60
  year: 2017
  ident: 10.1016/j.celrep.2019.03.047_bib59
  article-title: Genome-wide CRISPR screens reveal a Wnt-FZD5 signaling circuit as a druggable vulnerability of RNF43-mutant pancreatic tumors
  publication-title: Nat. Med.
  doi: 10.1038/nm.4219
– volume: 13
  start-page: 2498
  year: 2003
  ident: 10.1016/j.celrep.2019.03.047_bib53
  article-title: Cytoscape: a software environment for integrated models of biomolecular interaction networks
  publication-title: Genome Res.
  doi: 10.1101/gr.1239303
– volume: 9
  start-page: 417
  year: 2006
  ident: 10.1016/j.celrep.2019.03.047_bib66
  article-title: Mismatch repair proteins as sensors of alkylation DNA damage
  publication-title: Cancer Cell
  doi: 10.1016/j.ccr.2006.05.013
– volume: 107
  start-page: 11501
  year: 2010
  ident: 10.1016/j.celrep.2019.03.047_bib72
  article-title: Pattern of retinoblastoma pathway inactivation dictates response to CDK4/6 inhibition in GBM
  publication-title: Proc. Natl. Acad. Sci. USA
  doi: 10.1073/pnas.1001613107
– volume: 47
  start-page: 511
  year: 2012
  ident: 10.1016/j.celrep.2019.03.047_bib43
  article-title: Mcm8 and Mcm9 form a complex that functions in homologous recombination repair induced by DNA interstrand crosslinks
  publication-title: Mol. Cell
  doi: 10.1016/j.molcel.2012.05.047
– volume: 781
  start-page: 257
  year: 2011
  ident: 10.1016/j.celrep.2019.03.047_bib38
  article-title: Visualizing gene-set enrichment results using the Cytoscape plug-in enrichment map
  publication-title: Methods Mol. Biol.
  doi: 10.1007/978-1-61779-276-2_12
– volume: 13
  start-page: 2425
  year: 2015
  ident: 10.1016/j.celrep.2019.03.047_bib63
  article-title: Genome-wide CRISPR-Cas9 screens reveal loss of redundancy between PKMYT1 and WEE1 in glioblastoma stem-like cells
  publication-title: Cell Rep.
  doi: 10.1016/j.celrep.2015.11.021
– volume: 559
  start-page: 285
  year: 2018
  ident: 10.1016/j.celrep.2019.03.047_bib77
  article-title: CRISPR screens identify genomic ribonucleotides as a source of PARP-trapping lesions
  publication-title: Nature
  doi: 10.1038/s41586-018-0291-z
– volume: 15
  start-page: 550
  year: 2014
  ident: 10.1016/j.celrep.2019.03.047_bib34
  article-title: Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
  publication-title: Genome Biol.
  doi: 10.1186/s13059-014-0550-8
– volume: 343
  start-page: 84
  year: 2014
  ident: 10.1016/j.celrep.2019.03.047_bib55
  article-title: Genome-scale CRISPR-Cas9 knockout screening in human cells
  publication-title: Science
  doi: 10.1126/science.1247005
SSID ssj0000601194
Score 2.5827038
Snippet Glioblastoma therapies have remained elusive due to limitations in understanding mechanisms of growth and survival of the tumorigenic population. Using...
SourceID doaj
proquest
pubmed
crossref
elsevier
SourceType Open Website
Aggregation Database
Index Database
Enrichment Source
Publisher
StartPage 971
SubjectTerms CRISPR-Cas9
fitness genes
functional genomics
glioblastoma
glioblastoma stem cells
SummonAdditionalLinks – databaseName: DOAJ Directory of Open Access Journals
  dbid: DOA
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1La9wwEBYlUOil9N1NH6jQq6ltaSX7mC55tJBSskmbm5DkMbj4EWIvpD33h3fGspftoeylVyONhWY08w0afcPYeyc0QL7MInSQOpJK4ZmLJUTeC4cINvHJyLN9_kWdXcnP18vrnVZfVBMW6IHDxn1Ao0lKlevcKpDeKosRrYx97pzzNpFA3hdj3k4yFXwwcZnRlXKaUs1WKvX8bm4s7vJQ3wLRVSaB45S6q-zEpZG-_6_w9C_4OYahk0fs4YQf-VFY92N2D9on7H7oKPnzKft9Cm3XQPS9KoCvLj6tv15EK9vnfO2pwKbnx3c3XQ-c2KZRAv-2qYl2eqyQxZyZ27bg50Cvgau-6XlX8ktoul8ovSGJayp3D_0meNXy07rqHMLvoWssXw_Q8BXUdf-MXZ0cX67OoqnRQuSllkNkixyhgoNUY8jUaulTdHqYp0G6LFWqy6REnGjRt6VOOExpcGyBoT3zDtM1sczFc3bQdi28ZLyAOMc5mdcyl7KEDBR6CFXaUjiXCLlgYt5m4ycWcmqGUZu53OyHCcoxpBwTC4PKWbBoO-smsHDsGf-RNLgdSxza4we0LDNZltlnWQumZ_2bCY4EmIGiqj2_fzebi8HTSlcwtoVu0xuyRpFqmYkFexHsaLtIERM3X5Yf_o_Fv2IPaEF075Wo1-xguN3AG4RPg3s7npQ_drcWNQ
  priority: 102
  providerName: Directory of Open Access Journals
– databaseName: ScienceDirect
  dbid: IXB
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1La9wwEBYhUOil9N3tCxV6Nbu2tJJ9bEweLaSUOGn3JiTtuDj4say9kPTcH94ZP5bmUAI92kiy8YxmvrFmvmHsoxMaIFnGARpIHUilcM8tJATeC4cINvRhz7N9_lWdXckvq-XqgKVTLQylVY62f7DpvbUe78zHrznfFMU8izB2Qe-kEYLQaSQV_BJTCxXxrY72_1mIbyTs-yHS-IAmTBV0fZqXh3ILRFwZDmyn1GflLw_VE_nfcVT_AqK9Qzp5zB6NSJJ_Gl72CTuA-il7MPSWvH3Gfp9C3VQQ_CjWwNOLz9m3iyC1bcIzT6k2LT--2TQtcOKdxhX4911JBNR9rixGz9zWa34OVBdctFXLm5xfQtX8wtUrWjGjxPeh8wQvan5aFo1DIN41leVZBxVPoSzb5-zq5PgyPQvGlguBl1p2gV0nCBocRBqdp1ZLH6H5w4gNomWuIp2HOSJGi1YucsJhcINj1-jkY-8wcBPLRLxgh3VTwyvG17BIcE7stUykzCEGhbZC5TYXzoVCzpiYPrPxIx85tcUozZR4dm0G4RgSjlkIg8KZsWA_azPwcdwz_ogkuB9LbNr9jWb704zqZNAwhblKdGIVSG-VRdSUL3zinPM2lDBjepK_uaOcuFRxz-M_TOpicN_SYYytodm1hrRRRFrGYsZeDnq0f0mxIJa-OHn93899wx7SFR17heotO-y2O3iH6Klz7_vt8Qd-7hao
  priority: 102
  providerName: Elsevier
Title Genome-Wide CRISPR-Cas9 Screens Expose Genetic Vulnerabilities and Mechanisms of Temozolomide Sensitivity in Glioblastoma Stem Cells
URI https://dx.doi.org/10.1016/j.celrep.2019.03.047
https://www.ncbi.nlm.nih.gov/pubmed/30995489
https://www.proquest.com/docview/2211327483
https://doaj.org/article/0511f6979a6e4ca6a822f0c9bbbca14e
Volume 27
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwhV1Jb9QwFLZKEagXxM6wVEbiGpTEjp0cKkRH3ZAGoU4H5mbZzgsKytJOMlLLmR_Oc5YBJEa95JDYTpS3fS9--R4h7wyTAEkUe-ggpceFQJvzOXjWMoMINrBBx7M9-yxOF_zTMlrukLFn6_ACm_-mdq6f1GJVvL--uvmABn_wp1bLQrECxz4Z9JSlXN4hdzE2CafnswHw977ZcZzx8R-6LZP3yH3mO6I01_z9r3DVsfr_E7W2odIuOh0_JA8GWEk_9nrwiOxA9Zjc6xtN3jwhv06gqkvwvuUp0On52fzLuTfVTULn1tXdNPTo-rJugDoSalyBfl0Xjo26K5zFVJrqKqUzcD8J503Z0DqjF1DWP3H10q04d1XwfRsKmlf0pMhrg6i8rUtN5y2UdApF0Twli-Oji-mpN_Rf8CyXvPV0miCCMBBKjKRSRDZEX4jpG4RRJkKZBRnCR40uLzTMYKaDY1OM-LE1mMWxKGHPyG5VV_CC0BT8BOfEVvKE8wxiEOg4RKYzZkzA-ISw8TUrO5CTux4ZhRqr0H6oXk7KyUn5TKGcJsTbzLrsyTluGX_oJLgZ66i1uxP16rsaLFWhlwoykchEC-BWC40QKvNtYoyxOuAwIXKUvxpQSo8-cKn8ltu_HdVFoRG7nRldQb1uVIhpOAslj9mEPO_1aPOQoya-3HrlFdlzd3F7XIF4TXbb1RreIFRqzX73iQGPZ8vD_c4SfgO7ThHU
linkProvider Scholars Portal
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lj9MwELaWRQguiDflaSSuUZvYtZMjW-1uC9sV2nZhb5btTlBQHlXTSsCZH85MHhV7QCtxTfxSZjzzTTz-hrH3TmiAZBwHaCB1IJXCPTeSEHgvHCLY0IcNz_b8XE0v5cer8dUBm_R3YSitsrP9rU1vrHX3ZNh9zeE6y4aLCGMX9E4aIQidRsa32G1EA4ryumZXR_sfLUQ4EjYFEalDQD36K3RNnpeHfAPEXBm2dKdUaOUvF9Uw-V_zVP9Coo1HOnnA7ndQkn9oV_uQHUD5iN1pi0v-fMx-n0JZFRB8zVbAJxezxeeLYGLrhC885drU_PjHuqqBE_E0jsC_7HJioG6SZTF85rZc8TnQxeCsLmpepXwJRfULRy9oxAVlvrelJ3hW8tM8qxwi8W1VWL7YQsEnkOf1E3Z5crycTIOu5kLgpZbbwK4SRA0OIo3eU6uxj9D-YcgG0ThVkU7DFCGjRTMXOeEwusG2K_TysXcYuYlxIp6yw7Iq4TnjKxgl2Cf2WiZSphCDQmOhUpsK50IhB0z0n9n4jpCc6mLkps88-25a4RgSjhkJg8IZsGDfa90SctzQ_ogkuG9LdNrNg2rzzXT6ZNAyhalKdGIVSG-VRdiUjnzinPM2lDBgupe_uaadOFR2w_TvenUxuHHpNMaWUO1qQ9ooIi1jMWDPWj3aL1KMiKYvTl7897xv2d3pcn5mzmbnn16ye_SGzsBC9Yodbjc7eI1QauveNFvlD5VFGc8
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Genome-Wide+CRISPR-Cas9+Screens+Expose+Genetic+Vulnerabilities+and+Mechanisms+of+Temozolomide+Sensitivity+in+Glioblastoma+Stem+Cells&rft.jtitle=Cell+reports+%28Cambridge%29&rft.au=MacLeod%2C+Graham&rft.au=Bozek%2C+Danielle+A&rft.au=Rajakulendran%2C+Nishani&rft.au=Monteiro%2C+Vernon&rft.date=2019-04-16&rft.eissn=2211-1247&rft.volume=27&rft.issue=3&rft.spage=971&rft_id=info:doi/10.1016%2Fj.celrep.2019.03.047&rft_id=info%3Apmid%2F30995489&rft.externalDocID=30995489
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2211-1247&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2211-1247&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2211-1247&client=summon