Identifying biomarkers of heterogeneity and transplantation efficacy in retinal pigment epithelial cells

Transplantation of retinal pigment epithelial (RPE) cells holds great promise for patients with retinal degenerative diseases, such as age-related macular degeneration. In-depth characterization of RPE cell product identity and critical quality attributes are needed to enhance efficacy and safety of...

Full description

Saved in:
Bibliographic Details
Published inThe Journal of experimental medicine Vol. 220; no. 12
Main Authors Farjood, Farhad, Manos, Justine D, Wang, Yue, Williams, Anne L, Zhao, Cuiping, Borden, Susan, Alam, Nazia, Prusky, Glen, Temple, Sally, Stern, Jeffrey H, Boles, Nathan C
Format Journal Article
LanguageEnglish
Published United States Rockefeller University Press 04.12.2023
Subjects
Online AccessGet full text

Cover

Loading…
Abstract Transplantation of retinal pigment epithelial (RPE) cells holds great promise for patients with retinal degenerative diseases, such as age-related macular degeneration. In-depth characterization of RPE cell product identity and critical quality attributes are needed to enhance efficacy and safety of replacement therapy strategies. Here, we characterized an adult RPE stem cell-derived (RPESC-RPE) cell product using bulk and single-cell RNA sequencing (scRNA-seq), assessing functional cell integration in vitro into a mature RPE monolayer and in vivo efficacy by vision rescue in the Royal College of Surgeons rats. scRNA-seq revealed several distinct subpopulations in the RPESC-RPE product, some with progenitor markers. We identified RPE clusters expressing genes associated with in vivo efficacy and increased cell integration capability. Gene expression analysis revealed lncRNA (TREX) as a predictive marker of in vivo efficacy. TREX knockdown decreased cell integration while overexpression increased integration in vitro and improved vision rescue in the RCS rats.
AbstractList Transplantation of retinal pigment epithelial (RPE) cells holds great promise for patients with retinal degenerative diseases, such as age-related macular degeneration. In-depth characterization of RPE cell product identity and critical quality attributes are needed to enhance efficacy and safety of replacement therapy strategies. Here, we characterized an adult RPE stem cell-derived (RPESC-RPE) cell product using bulk and single-cell RNA sequencing (scRNA-seq), assessing functional cell integration in vitro into a mature RPE monolayer and in vivo efficacy by vision rescue in the Royal College of Surgeons rats. scRNA-seq revealed several distinct subpopulations in the RPESC-RPE product, some with progenitor markers. We identified RPE clusters expressing genes associated with in vivo efficacy and increased cell integration capability. Gene expression analysis revealed lncRNA (TREX) as a predictive marker of in vivo efficacy. TREX knockdown decreased cell integration while overexpression increased integration in vitro and improved vision rescue in the RCS rats.
This study characterizes an adult retinal pigment epithelial stem cell–derived cell product through transplantation in RCS rats and bulk and single-cell RNA sequencing, identifying distinct subpopulations and a predictive lncRNA marker (TREX) affecting cell integration and vision rescue in rats. Transplantation of retinal pigment epithelial (RPE) cells holds great promise for patients with retinal degenerative diseases, such as age-related macular degeneration. In-depth characterization of RPE cell product identity and critical quality attributes are needed to enhance efficacy and safety of replacement therapy strategies. Here, we characterized an adult RPE stem cell–derived (RPESC-RPE) cell product using bulk and single-cell RNA sequencing (scRNA-seq), assessing functional cell integration in vitro into a mature RPE monolayer and in vivo efficacy by vision rescue in the Royal College of Surgeons rats. scRNA-seq revealed several distinct subpopulations in the RPESC-RPE product, some with progenitor markers. We identified RPE clusters expressing genes associated with in vivo efficacy and increased cell integration capability. Gene expression analysis revealed lncRNA (TREX) as a predictive marker of in vivo efficacy. TREX knockdown decreased cell integration while overexpression increased integration in vitro and improved vision rescue in the RCS rats.
Author Zhao, Cuiping
Wang, Yue
Temple, Sally
Manos, Justine D
Prusky, Glen
Alam, Nazia
Boles, Nathan C
Williams, Anne L
Farjood, Farhad
Stern, Jeffrey H
Borden, Susan
AuthorAffiliation 1 https://ror.org/00x6sm138 Neural Stem Cell Institute , Rensselaer, NY, USA
3 Abbvie, Cambridge Research Center , Cambridge, MA, USA
2 https://ror.org/02r109517 Burke Neurological Institute at Weill Cornell Medicine , White Plains, NY, USA
4 Regeneron , Rensselaer, NY, USA
AuthorAffiliation_xml – name: 1 https://ror.org/00x6sm138 Neural Stem Cell Institute , Rensselaer, NY, USA
– name: 2 https://ror.org/02r109517 Burke Neurological Institute at Weill Cornell Medicine , White Plains, NY, USA
– name: 3 Abbvie, Cambridge Research Center , Cambridge, MA, USA
– name: 4 Regeneron , Rensselaer, NY, USA
Author_xml – sequence: 1
  givenname: Farhad
  orcidid: 0000-0002-8826-6721
  surname: Farjood
  fullname: Farjood, Farhad
  organization: Neural Stem Cell Institute , Rensselaer, NY, USA
– sequence: 2
  givenname: Justine D
  orcidid: 0000-0002-4265-4016
  surname: Manos
  fullname: Manos, Justine D
  organization: Abbvie, Cambridge Research Center, Cambridge, MA, USA
– sequence: 3
  givenname: Yue
  orcidid: 0009-0007-6647-3379
  surname: Wang
  fullname: Wang, Yue
  organization: Neural Stem Cell Institute , Rensselaer, NY, USA
– sequence: 4
  givenname: Anne L
  orcidid: 0000-0002-2491-5294
  surname: Williams
  fullname: Williams, Anne L
  organization: Neural Stem Cell Institute , Rensselaer, NY, USA
– sequence: 5
  givenname: Cuiping
  orcidid: 0009-0003-3885-7093
  surname: Zhao
  fullname: Zhao, Cuiping
  organization: Regeneron, Rensselaer, NY, USA
– sequence: 6
  givenname: Susan
  orcidid: 0009-0001-2361-1686
  surname: Borden
  fullname: Borden, Susan
  organization: Neural Stem Cell Institute , Rensselaer, NY, USA
– sequence: 7
  givenname: Nazia
  orcidid: 0000-0002-1941-2190
  surname: Alam
  fullname: Alam, Nazia
  organization: Burke Neurological Institute at Weill Cornell Medicine , White Plains, NY, USA
– sequence: 8
  givenname: Glen
  orcidid: 0000-0001-9658-8598
  surname: Prusky
  fullname: Prusky, Glen
  organization: Burke Neurological Institute at Weill Cornell Medicine , White Plains, NY, USA
– sequence: 9
  givenname: Sally
  orcidid: 0000-0001-7301-783X
  surname: Temple
  fullname: Temple, Sally
  organization: Neural Stem Cell Institute , Rensselaer, NY, USA
– sequence: 10
  givenname: Jeffrey H
  orcidid: 0000-0002-5272-5025
  surname: Stern
  fullname: Stern, Jeffrey H
  organization: Neural Stem Cell Institute , Rensselaer, NY, USA
– sequence: 11
  givenname: Nathan C
  orcidid: 0000-0002-9253-9411
  surname: Boles
  fullname: Boles, Nathan C
  organization: Neural Stem Cell Institute , Rensselaer, NY, USA
BackLink https://www.ncbi.nlm.nih.gov/pubmed/37728563$$D View this record in MEDLINE/PubMed
BookMark eNpVUUtL7DAUDqLo-Ni5vmR5F1ZPmqZpV3IRXyC40XVI09OZaJv0Jhlh_r0ZfKCrA-d853vwHZJd5x0ScsrgnEFTXbzgdF5CyaFlfIcsmKigaAVvdskCoCwLBiAPyGGMLwCsqkS9Tw64lGUjar4gq_seXbLDxrol7ayfdHjFEKkf6AoTBr9EhzZtqHY9TUG7OI_aJZ2sdxSHwRptNtQ6GjBZp0c62-WUGSnONq1wtHllcBzjMdkb9Bjx5HMekeeb66eru-Lh8fb-6t9DYThUqWgH2fWScS56I8qG8Q5YIwRAq5F1bVlj1fIasRXQ5RBoOoGG10b2-ZNxyY_I5QfvvO4m7E32EvSo5mBztI3y2qrfF2dXaunfFAPBQPI6M_z9ZAj-_xpjUpON2wzaoV9HVTZ1LUUD1Vbs7ANqgo8x4PCtw0Bt21G5HfXVTob_-entG_xVB38HAKSPjg
Cites_doi 10.1038/nbt.4114
10.1126/science.1076997
10.1186/s13059-019-1874-1
10.1016/j.exer.2014.11.001
10.1016/j.ymthe.2017.06.002
10.1074/jbc.M800706200
10.1056/NEJMoa1608368
10.3389/fimmu.2016.00172
10.1167/iovs.10-6163
10.1371/journal.pone.0141597
10.1172/jci.insight.129299
10.1073/pnas.2117553119
10.17912/micropub.biology.000811
10.1182/blood-2005-09-3585
10.1073/pnas.1914143116
10.1073/pnas.0813144106
10.1093/bioinformatics/bts635
10.1101/2020.01.13.904730
10.1093/hmg/ddq129
10.1093/bioinformatics/btq046
10.1016/j.stemcr.2022.05.005
10.1038/s42003-022-03676-3
10.1152/physrev.00021.2004
10.1167/iovs.06-0868
10.1016/j.stem.2011.11.018
10.1038/s41467-020-14457-z
10.1016/j.biochi.2004.09.029
10.2174/156652410793937813
10.3791/55220
10.1167/iovs.04-0541
10.3389/fcell.2021.802457
10.1186/s12950-015-0109-9
10.1017/S0952523805225166
10.2217/bmm-2018-0272
10.1016/j.stemcr.2017.05.016
10.1371/journal.pone.0038673
10.1161/CIRCRESAHA.111.249433
10.1186/gb-2010-11-2-r14
10.1126/scitranslmed.aat5580
ContentType Journal Article
Copyright 2023 Farjood et al.
2023 Farjood et al. 2023 Farjood et al.
Copyright_xml – notice: 2023 Farjood et al.
– notice: 2023 Farjood et al. 2023 Farjood et al.
DBID CGR
CUY
CVF
ECM
EIF
NPM
AAYXX
CITATION
7X8
5PM
DOI 10.1084/jem.20230913
DatabaseName Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
CrossRef
MEDLINE - Academic
PubMed Central (Full Participant titles)
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
CrossRef
MEDLINE - Academic
DatabaseTitleList MEDLINE - Academic
MEDLINE
CrossRef

Database_xml – sequence: 1
  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
– sequence: 2
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Medicine
DocumentTitleAlternate RPE biomarkers of transplant efficacy
EISSN 1540-9538
ExternalDocumentID 10_1084_jem_20230913
37728563
Genre Research Support, Non-U.S. Gov't
Journal Article
Research Support, N.I.H., Extramural
GrantInformation_xml – fundername: NIH HHS
  grantid: R01EY032138
– fundername: NEI NIH HHS
  grantid: R01 EY032138
– fundername: NEI NIH HHS
  grantid: R01 EY029281
– fundername: NEI NIH HHS
  grantid: U01 EY030581
– fundername: NEI NIH HHS
  grantid: R01 EY022079
– fundername: ;
  grantid: R01EY032138; R01EY029281; U01EY030581
– fundername: ;
– fundername: ;
  grantid: C028504
GroupedDBID ---
-~X
18M
29K
2WC
36B
4.4
53G
5GY
5RE
5VS
ABOCM
ABZEH
ACGFO
ACNCT
ACPRK
ADBBV
AENEX
AFOSN
AFRAH
ALMA_UNASSIGNED_HOLDINGS
AOIJS
BAWUL
BTFSW
C45
CGR
CS3
CUY
CVF
D-I
DIK
DU5
E3Z
EBS
ECM
EIF
EMB
F5P
F9R
FRP
GX1
HYE
IH2
KQ8
L7B
N9A
NPM
O5R
O5S
OK1
P2P
P6G
R.V
RHF
RHI
RPM
SJN
TR2
TRP
UHB
W8F
WOQ
AAYXX
CITATION
7X8
5PM
ID FETCH-LOGICAL-c304t-9f7bd71335dc52813b01855009ae1b926e4936ee950b772ecb5ec36c7d9f71373
ISSN 0022-1007
IngestDate Tue Sep 17 21:29:13 EDT 2024
Sat Oct 26 06:02:23 EDT 2024
Thu Nov 21 21:19:56 EST 2024
Sat Nov 02 12:31:57 EDT 2024
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 12
Language English
License 2023 Farjood et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
LinkModel OpenURL
MergedId FETCHMERGED-LOGICAL-c304t-9f7bd71335dc52813b01855009ae1b926e4936ee950b772ecb5ec36c7d9f71373
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
C. Zhao’s current affiliation is Regeneron Pharmaceuticals, Rensselaer, NY, USA.
J.H. Stern and N.C. Boles are co-senior authors.
Disclosures: J.D. Manos is currently an employee at AbbVie. G. Prusky is the president of CerebralMechanics Inc. Equipment used in the study was manufactured by CerebralMechanics. She had no influence on how the data the study was generated. S. Temple reported a patent to US8481313B2 issued; and is a co-founder of LUXA Biotechnology, which is advancing RPE transplantation for patients with dry age-related macular degeneration (AMD). J.H. Stern is an officer of Luxa Biotechnology, which is advancing retinal pigment epithelial cell transplantation therapy for dry age-related macular degeneration. No other disclosures were reported.
J.D. Manos’s current affiliation is Abbvie, Cambridge Research Center, Cambridge, MA, USA.
ORCID 0000-0002-5272-5025
0009-0001-2361-1686
0000-0001-9658-8598
0000-0002-4265-4016
0000-0001-7301-783X
0009-0007-6647-3379
0009-0003-3885-7093
0000-0002-9253-9411
0000-0002-1941-2190
0000-0002-2491-5294
0000-0002-8826-6721
OpenAccessLink https://pubmed.ncbi.nlm.nih.gov/PMC10510736
PMID 37728563
PQID 2866758047
PQPubID 23479
ParticipantIDs pubmedcentral_primary_oai_pubmedcentral_nih_gov_10510736
proquest_miscellaneous_2866758047
crossref_primary_10_1084_jem_20230913
pubmed_primary_37728563
PublicationCentury 2000
PublicationDate 2023-12-04
PublicationDateYYYYMMDD 2023-12-04
PublicationDate_xml – month: 12
  year: 2023
  text: 2023-12-04
  day: 04
PublicationDecade 2020
PublicationPlace United States
PublicationPlace_xml – name: United States
PublicationTitle The Journal of experimental medicine
PublicationTitleAlternate J Exp Med
PublicationYear 2023
Publisher Rockefeller University Press
Publisher_xml – name: Rockefeller University Press
References da Cruz (2023092013362726000_bib6) 2018; 36
Prusky (2023092013362726000_bib26) 2004; 45
Petrus-Reurer (2023092013362726000_bib24) 2022; 17
Liang (2023092013362726000_bib17) 2017; 25
Cavallaro (2023092013362726000_bib4) 1990; 31
Sparrow (2023092013362726000_bib30) 2010; 10
Young (2023092013362726000_bib38) 2010; 11
Kopitz (2023092013362726000_bib14) 2004; 86
Lu (2023092013362726000_bib19) 2016; 13
Wong (2023092013362726000_bib36) 2019; 5
Zhao (2023092013362726000_bib40) 2017
Voigt (2023092013362726000_bib34) 2019; 116
Cao (2023092013362726000_bib3) 2002; 298
Pfeffer (2023092013362726000_bib25) 2004; 10
Davis (2023092013362726000_bib7) 2017; 9
Salero (2023092013362726000_bib27) 2012; 10
Sharma (2023092013362726000_bib29) 2019; 11
Dobin (2023092013362726000_bib8) 2013; 29
Vives-Bauza (2023092013362726000_bib33) 2008; 283
Augsten (2023092013362726000_bib1) 2009; 106
Gu (2023092013362726000_bib10) 2012; 7
Lee (2023092013362726000_bib15) 2022; 5
Bennis (2023092013362726000_bib2) 2015; 10
Karantanos (2023092013362726000_bib13) 2016; 7
Kamminga (2023092013362726000_bib12) 2006; 107
Lin (2023092013362726000_bib18) 2011; 52
Ortolan (2023092013362726000_bib22) 2022; 119
Hafemeister (2023092013362726000_bib11) 2019; 20
2023092013362726000_bib39
Zou (2023092013362726000_bib41) 2019; 13
Cuomo (2023092013362726000_bib5) 2020; 11
Douglas (2023092013362726000_bib9) 2005; 22
Lee (2023092013362726000_bib16) 2011; 109
Sayols (2023092013362726000_bib28) 2020
Mandai (2023092013362726000_bib20) 2017; 376
Xu (2023092013362726000_bib37) 2021; 9
Pau (2023092013362726000_bib23) 2010; 26
Strunnikova (2023092013362726000_bib32) 2010; 19
Strauss (2023092013362726000_bib31) 2005; 85
Mullins (2023092013362726000_bib21) 2007; 48
Whitmore (2023092013362726000_bib35) 2014; 129
References_xml – volume: 36
  start-page: 328
  year: 2018
  ident: 2023092013362726000_bib6
  article-title: Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration
  publication-title: Nat. Biotechnol.
  doi: 10.1038/nbt.4114
  contributor:
    fullname: da Cruz
– volume: 298
  start-page: 1039
  year: 2002
  ident: 2023092013362726000_bib3
  article-title: Role of histone H3 lysine 27 methylation in Polycomb-group silencing
  publication-title: Science
  doi: 10.1126/science.1076997
  contributor:
    fullname: Cao
– volume: 20
  start-page: 296
  year: 2019
  ident: 2023092013362726000_bib11
  article-title: Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression
  publication-title: Genome Biol.
  doi: 10.1186/s13059-019-1874-1
  contributor:
    fullname: Hafemeister
– volume: 129
  start-page: 93
  year: 2014
  ident: 2023092013362726000_bib35
  article-title: Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq
  publication-title: Exp. Eye Res.
  doi: 10.1016/j.exer.2014.11.001
  contributor:
    fullname: Whitmore
– volume: 25
  start-page: 2075
  year: 2017
  ident: 2023092013362726000_bib17
  article-title: RNase H1-dependent antisense oligonucleotides are robustly active in directing RNA cleavage in both the cytoplasm and the nucleus
  publication-title: Mol. Ther.
  doi: 10.1016/j.ymthe.2017.06.002
  contributor:
    fullname: Liang
– volume: 283
  start-page: 24770
  year: 2008
  ident: 2023092013362726000_bib33
  article-title: The age lipid A2E and mitochondrial dysfunction synergistically impair phagocytosis by retinal pigment epithelial cells
  publication-title: J. Biol. Chem.
  doi: 10.1074/jbc.M800706200
  contributor:
    fullname: Vives-Bauza
– volume: 376
  start-page: 1038
  year: 2017
  ident: 2023092013362726000_bib20
  article-title: Autologous induced stem-cell-derived retinal cells for macular degeneration
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMoa1608368
  contributor:
    fullname: Mandai
– volume: 7
  start-page: 172
  year: 2016
  ident: 2023092013362726000_bib13
  article-title: Regulation of T Cell differentiation and function by EZH2
  publication-title: Front. Immunol.
  doi: 10.3389/fimmu.2016.00172
  contributor:
    fullname: Karantanos
– volume: 52
  start-page: 3521
  year: 2011
  ident: 2023092013362726000_bib18
  article-title: Mitochondrial DNA damage and repair in RPE associated with aging and age-related macular degeneration
  publication-title: Invest. Ophthalmol. Vis. Sci.
  doi: 10.1167/iovs.10-6163
  contributor:
    fullname: Lin
– volume: 10
  year: 2015
  ident: 2023092013362726000_bib2
  article-title: Comparison of mouse and human retinal pigment epithelium gene expression profiles: Potential implications for age-related macular degeneration
  publication-title: PLoS One
  doi: 10.1371/journal.pone.0141597
  contributor:
    fullname: Bennis
– volume: 5
  year: 2019
  ident: 2023092013362726000_bib36
  article-title: The long noncoding RNA MALAT1 predicts human pancreatic islet isolation quality
  publication-title: JCI insight
  doi: 10.1172/jci.insight.129299
  contributor:
    fullname: Wong
– volume: 10
  start-page: 23
  year: 2004
  ident: 2023092013362726000_bib25
  article-title: Expression of transthyretin and retinol binding protein mRNAs and secretion of transthyretin by cultured monkey retinal pigment epithelium
  publication-title: Mol. Vis.
  contributor:
    fullname: Pfeffer
– volume: 119
  year: 2022
  ident: 2023092013362726000_bib22
  article-title: Single-cell-resolution map of human retinal pigment epithelium helps discover subpopulations with differential disease sensitivity
  publication-title: Proc. Natl. Acad. Sci. USA
  doi: 10.1073/pnas.2117553119
  contributor:
    fullname: Ortolan
– year: 2020
  ident: 2023092013362726000_bib28
  article-title: rrvgo: A Bioconductor package to reduce and visualize Gene Ontology terms
  publication-title: MicroPubl. Biol.
  doi: 10.17912/micropub.biology.000811
  contributor:
    fullname: Sayols
– volume: 107
  start-page: 2170
  year: 2006
  ident: 2023092013362726000_bib12
  article-title: The Polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion
  publication-title: Blood
  doi: 10.1182/blood-2005-09-3585
  contributor:
    fullname: Kamminga
– volume: 116
  start-page: 24100
  year: 2019
  ident: 2023092013362726000_bib34
  article-title: Single-cell transcriptomics of the human retinal pigment epithelium and choroid in health and macular degeneration
  publication-title: Proc. Natl. Acad. Sci. USA
  doi: 10.1073/pnas.1914143116
  contributor:
    fullname: Voigt
– volume: 106
  start-page: 3414
  year: 2009
  ident: 2023092013362726000_bib1
  article-title: CXCL14 is an autocrine growth factor for fibroblasts and acts as a multi-modal stimulator of prostate tumor growth
  publication-title: Proc. Natl. Acad. Sci. USA
  doi: 10.1073/pnas.0813144106
  contributor:
    fullname: Augsten
– volume: 29
  start-page: 15
  year: 2013
  ident: 2023092013362726000_bib8
  article-title: STAR: Ultrafast universal RNA-seq aligner
  publication-title: Bioinformatics
  doi: 10.1093/bioinformatics/bts635
  contributor:
    fullname: Dobin
– ident: 2023092013362726000_bib39
  doi: 10.1101/2020.01.13.904730
– volume: 19
  start-page: 2468
  year: 2010
  ident: 2023092013362726000_bib32
  article-title: Transcriptome analysis and molecular signature of human retinal pigment epithelium
  publication-title: Hum. Mol. Genet.
  doi: 10.1093/hmg/ddq129
  contributor:
    fullname: Strunnikova
– volume: 26
  start-page: 979
  year: 2010
  ident: 2023092013362726000_bib23
  article-title: EBImage: An R package for image processing with applications to cellular phenotypes
  publication-title: Bioinformatics
  doi: 10.1093/bioinformatics/btq046
  contributor:
    fullname: Pau
– volume: 17
  start-page: 1458
  year: 2022
  ident: 2023092013362726000_bib24
  article-title: Molecular profiling of stem cell-derived retinal pigment epithelial cell differentiation established for clinical translation
  publication-title: Stem Cell Rep.
  doi: 10.1016/j.stemcr.2022.05.005
  contributor:
    fullname: Petrus-Reurer
– volume: 5
  start-page: 722
  year: 2022
  ident: 2023092013362726000_bib15
  article-title: Single-cell transcriptome of the mouse retinal pigment epithelium in response to a low-dose of doxorubicin
  publication-title: Commun. Biol.
  doi: 10.1038/s42003-022-03676-3
  contributor:
    fullname: Lee
– volume: 31
  start-page: 497
  year: 1990
  ident: 2023092013362726000_bib4
  article-title: The retinal pigment epithelium is the unique site of transthyretin synthesis in the rat eye
  publication-title: Invest. Ophthalmol. Vis. Sci.
  contributor:
    fullname: Cavallaro
– volume: 85
  start-page: 845
  year: 2005
  ident: 2023092013362726000_bib31
  article-title: The retinal pigment epithelium in visual function
  publication-title: Physiol. Rev.
  doi: 10.1152/physrev.00021.2004
  contributor:
    fullname: Strauss
– volume: 48
  start-page: 3372
  year: 2007
  ident: 2023092013362726000_bib21
  article-title: Differential macular and peripheral expression of bestrophin in human eyes and its implication for best disease
  publication-title: Invest. Ophthalmol. Vis. Sci.
  doi: 10.1167/iovs.06-0868
  contributor:
    fullname: Mullins
– volume: 10
  start-page: 88
  year: 2012
  ident: 2023092013362726000_bib27
  article-title: Adult human RPE can be activated into a multipotent stem cell that produces mesenchymal derivatives
  publication-title: Cell Stem Cell
  doi: 10.1016/j.stem.2011.11.018
  contributor:
    fullname: Salero
– volume: 11
  start-page: 810
  year: 2020
  ident: 2023092013362726000_bib5
  article-title: Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression
  publication-title: Nat. Commun.
  doi: 10.1038/s41467-020-14457-z
  contributor:
    fullname: Cuomo
– volume: 86
  start-page: 825
  year: 2004
  ident: 2023092013362726000_bib14
  article-title: Lipids and lipid peroxidation products in the pathogenesis of age-related macular degeneration
  publication-title: Biochimie
  doi: 10.1016/j.biochi.2004.09.029
  contributor:
    fullname: Kopitz
– volume: 10
  start-page: 802
  year: 2010
  ident: 2023092013362726000_bib30
  article-title: The retinal pigment epithelium in health and disease
  publication-title: Curr. Mol. Med.
  doi: 10.2174/156652410793937813
  contributor:
    fullname: Sparrow
– start-page: 55220
  year: 2017
  ident: 2023092013362726000_bib40
  article-title: Development of a refined protocol for trans-scleral subretinal transplantation of human retinal pigment epithelial cells into rat eyes
  publication-title: J. Vis. Exp.
  doi: 10.3791/55220
  contributor:
    fullname: Zhao
– volume: 45
  start-page: 4611
  year: 2004
  ident: 2023092013362726000_bib26
  article-title: Rapid quantification of adult and developing mouse spatial vision using a virtual optomotor system
  publication-title: Invest. Ophthalmol. Vis. Sci.
  doi: 10.1167/iovs.04-0541
  contributor:
    fullname: Prusky
– volume: 9
  start-page: 802457
  year: 2021
  ident: 2023092013362726000_bib37
  article-title: A single-cell transcriptome atlas of the human retinal pigment epithelium
  publication-title: Front. Cell Dev. Biol.
  doi: 10.3389/fcell.2021.802457
  contributor:
    fullname: Xu
– volume: 13
  start-page: 1
  year: 2016
  ident: 2023092013362726000_bib19
  article-title: CXCL14 as an emerging immune and inflammatory modulator
  publication-title: J. Inflamm.
  doi: 10.1186/s12950-015-0109-9
  contributor:
    fullname: Lu
– volume: 22
  start-page: 677
  year: 2005
  ident: 2023092013362726000_bib9
  article-title: Independent visual threshold measurements in the two eyes of freely moving rats and mice using a virtual-reality optokinetic system
  publication-title: Vis. Neurosci.
  doi: 10.1017/S0952523805225166
  contributor:
    fullname: Douglas
– volume: 13
  start-page: 185
  year: 2019
  ident: 2023092013362726000_bib41
  article-title: Analysis of long noncoding RNAs for acute rejection and graft outcome in kidney transplant biopsies
  publication-title: Biomarkers Med.
  doi: 10.2217/bmm-2018-0272
  contributor:
    fullname: Zou
– volume: 9
  start-page: 42
  year: 2017
  ident: 2023092013362726000_bib7
  article-title: The developmental stage of adult human stem cell-derived retinal pigment epithelium cells influences transplant efficacy for vision rescue
  publication-title: Stem Cell Rep.
  doi: 10.1016/j.stemcr.2017.05.016
  contributor:
    fullname: Davis
– volume: 7
  year: 2012
  ident: 2023092013362726000_bib10
  article-title: Age-related changes in the retinal pigment epithelium (RPE)
  publication-title: PLoS One
  doi: 10.1371/journal.pone.0038673
  contributor:
    fullname: Gu
– volume: 109
  start-page: 1332
  year: 2011
  ident: 2023092013362726000_bib16
  article-title: Analysis of transcriptome complexity through RNA sequencing in normal and failing murine hearts
  publication-title: Circ. Res.
  doi: 10.1161/CIRCRESAHA.111.249433
  contributor:
    fullname: Lee
– volume: 11
  start-page: R14
  year: 2010
  ident: 2023092013362726000_bib38
  article-title: Gene ontology analysis for RNA-seq: Accounting for selection bias
  publication-title: Genome Biol.
  doi: 10.1186/gb-2010-11-2-r14
  contributor:
    fullname: Young
– volume: 11
  year: 2019
  ident: 2023092013362726000_bib29
  article-title: Clinical-grade stem cell-derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs
  publication-title: Sci. Transl. Med.
  doi: 10.1126/scitranslmed.aat5580
  contributor:
    fullname: Sharma
SSID ssj0014456
Score 2.4858537
Snippet Transplantation of retinal pigment epithelial (RPE) cells holds great promise for patients with retinal degenerative diseases, such as age-related macular...
This study characterizes an adult retinal pigment epithelial stem cell–derived cell product through transplantation in RCS rats and bulk and single-cell RNA...
SourceID pubmedcentral
proquest
crossref
pubmed
SourceType Open Access Repository
Aggregation Database
Index Database
SubjectTerms Animals
Biomarkers
Epithelial Cells
Gene Expression Profiling
Neurons
Neuroscience
Rats
Retinal Pigments
Stem Cells & Regeneration
Title Identifying biomarkers of heterogeneity and transplantation efficacy in retinal pigment epithelial cells
URI https://www.ncbi.nlm.nih.gov/pubmed/37728563
https://search.proquest.com/docview/2866758047
https://pubmed.ncbi.nlm.nih.gov/PMC10510736
Volume 220
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lj9MwELbKIq32gnhTXjISnFBKYjsPH1cLywpRhNCuVE5R7Li0aEmrNr3wh_ibzDhO4nT3AHuJrDSOo5mv45nxPAh5DXtMlvJIBbJgMRbV1jCKkqBkXOlIsTK27YCmX5KzC_FpFs9Goz9e1NKuVhP9-9q8kptwFe4BXzFL9j84270UbsAY-AtX4DBc_4nHTZZtk6mEefQYarPZNvof0GsFEw1q2TZK0lYxvywqF15osHYE9nq3CS21bY61Xv6wsQFmjZkal-hMR8f-1tdg-1wyq8UOOgTsH9SfFpufLqQHhoui7P3fLrzPNhMDPff9pPfsN9Ln-64_NfJ8QsewL7z9PPGdFYzbwI_eWfkNZLyZ44nE5kompC-lwUDG6I1mj3KCWYR41Jz5kpux0Icou3ZLCDOBW4LBsgNgb8km9dVDx_qXhQcHOyOLnbQd1OX-Oj2JUHalPLlFbmPFRWzS8HHWxRKBUWrbBHcf7jIsYOl3_sJH5LBdZagGXbFt9kN0PZ3n_C6549hMjxvk3SMjU90nh1PH5Qdk4QGQ9gCkqzkdAJACAOkeAGkLQLqsqAMgdQCkPQCpBeBDcnH64fzkLHCtOwLNQ1EHcp6qEv0fcaljlkVchRGWzgtlYSIlWWKE5IkxMg4VUMRoFRvNE52WMDPiKX9EDqpVZZ4QKkxpdFzCu6QQpUxkCjIEGyfAU-Fc6jF501IyXzcVWnIbWZGJHIift8Qfk1ctmXMQofj1RWVWu23OsgTN5lCkY_K4IXv3ppZfY5INGNI9gOXZh79Uy4Ut095i5unNpz4jR_2_6Dk5qDc78wKU4Fq9tAD8C-xjuLU
link.rule.ids 230,314,780,784,885,27924,27925
linkProvider Geneva Foundation for Medical Education and Research
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=Identifying+biomarkers+of+heterogeneity+and+transplantation+efficacy+in+retinal+pigment+epithelial+cells&rft.jtitle=The+Journal+of+experimental+medicine&rft.au=Farjood%2C+Farhad&rft.au=Manos%2C+Justine+D.&rft.au=Wang%2C+Yue&rft.au=Williams%2C+Anne+L.&rft.date=2023-12-04&rft.pub=Rockefeller+University+Press&rft.issn=0022-1007&rft.eissn=1540-9538&rft.volume=220&rft.issue=12&rft_id=info:doi/10.1084%2Fjem.20230913&rft_id=info%3Apmid%2F37728563&rft.externalDBID=PMC10510736
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0022-1007&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0022-1007&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0022-1007&client=summon