Decoding molecular markers and transcriptional circuitry of naive and primed states of human pluripotency
•WGCNA used to identify molecular markers in naive and primed states of human pluripotency.•Naive genes were involved in metabolic processes and primed genes in system development.•Identified 52 and 33 TFs as crucial to naive and primed states, respectively.•The TFs might play a switch on-off mechan...
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Published in | Stem cell research Vol. 53; p. 102334 |
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Main Authors | , |
Format | Journal Article |
Language | English |
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Elsevier B.V
01.05.2021
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Abstract | •WGCNA used to identify molecular markers in naive and primed states of human pluripotency.•Naive genes were involved in metabolic processes and primed genes in system development.•Identified 52 and 33 TFs as crucial to naive and primed states, respectively.•The TFs might play a switch on-off mechanism in induction of the pluripotent states.•Four newly identified molecular markers are MSANTD3, SP4, ZNF232, and ZNF275.
Pluripotent stem cells (PSCs) have been observed to occur in two distinct states — naive and primed. Both naive and primed state PSCs can give rise to tissues of all the three germ layers in vitro but differ in their potential to generate germline chimera in vivo. Understanding the molecular mechanisms that govern these two states of pluripotency in human can open a plethora of opportunities for studying early embryonic development and in biomedical applications. In this work, we use weighted gene co-expression network analysis (WGCNA) to identify the key molecular makers and their interactions that define the two distinct pluripotency states. Signed hybrid network was reconstructed from transcriptomic data (RNA-seq) of naive and primed state pluripotent samples. Our analysis revealed two sets of genes that are involved in the establishment and maintenance of naive and primed states. The naive state genes were found to be enriched for biological processes and pathways related to metabolic processes while primed state genes were associated with system development. We further filtered these lists to identify the intra-modular hubs and the hub transcription factors (TFs) for each group. Validation of the identified TFs was carried out using independent microarray datasets and we finally present a list of 52 and 33 TFs as the set of core TFs that are responsible for the induction and maintenance of naive and primed states of pluripotency in human, respectively. Among these, the TFs ZNF275, ZNF232, SP4, and MSANTD3 could be of interest as they were not reported in previous studies. |
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AbstractList | Pluripotent stem cells (PSCs) have been observed to occur in two distinct states - naive and primed. Both naive and primed state PSCs can give rise to tissues of all the three germ layers in vitro but differ in their potential to generate germline chimera in vivo. Understanding the molecular mechanisms that govern these two states of pluripotency in human can open a plethora of opportunities for studying early embryonic development and in biomedical applications. In this work, we use weighted gene co-expression network analysis (WGCNA) to identify the key molecular makers and their interactions that define the two distinct pluripotency states. Signed hybrid network was reconstructed from transcriptomic data (RNA-seq) of naive and primed state pluripotent samples. Our analysis revealed two sets of genes that are involved in the establishment and maintenance of naive and primed states. The naive state genes were found to be enriched for biological processes and pathways related to metabolic processes while primed state genes were associated with system development. We further filtered these lists to identify the intra-modular hubs and the hub transcription factors (TFs) for each group. Validation of the identified TFs was carried out using independent microarray datasets and we finally present a list of 52 and 33 TFs as the set of core TFs that are responsible for the induction and maintenance of naive and primed states of pluripotency in human, respectively. Among these, the TFs ZNF275, ZNF232, SP4, and MSANTD3 could be of interest as they were not reported in previous studies. •WGCNA used to identify molecular markers in naive and primed states of human pluripotency.•Naive genes were involved in metabolic processes and primed genes in system development.•Identified 52 and 33 TFs as crucial to naive and primed states, respectively.•The TFs might play a switch on-off mechanism in induction of the pluripotent states.•Four newly identified molecular markers are MSANTD3, SP4, ZNF232, and ZNF275. Pluripotent stem cells (PSCs) have been observed to occur in two distinct states — naive and primed. Both naive and primed state PSCs can give rise to tissues of all the three germ layers in vitro but differ in their potential to generate germline chimera in vivo. Understanding the molecular mechanisms that govern these two states of pluripotency in human can open a plethora of opportunities for studying early embryonic development and in biomedical applications. In this work, we use weighted gene co-expression network analysis (WGCNA) to identify the key molecular makers and their interactions that define the two distinct pluripotency states. Signed hybrid network was reconstructed from transcriptomic data (RNA-seq) of naive and primed state pluripotent samples. Our analysis revealed two sets of genes that are involved in the establishment and maintenance of naive and primed states. The naive state genes were found to be enriched for biological processes and pathways related to metabolic processes while primed state genes were associated with system development. We further filtered these lists to identify the intra-modular hubs and the hub transcription factors (TFs) for each group. Validation of the identified TFs was carried out using independent microarray datasets and we finally present a list of 52 and 33 TFs as the set of core TFs that are responsible for the induction and maintenance of naive and primed states of pluripotency in human, respectively. Among these, the TFs ZNF275, ZNF232, SP4, and MSANTD3 could be of interest as they were not reported in previous studies. |
ArticleNumber | 102334 |
Author | Ghosh, Arindam Som, Anup |
Author_xml | – sequence: 1 givenname: Arindam surname: Ghosh fullname: Ghosh, Arindam organization: Centre of Bioinformatics, Institute of Interdisciplinary Studies, University of Allahabad, Prayagraj 211002, India – sequence: 2 givenname: Anup surname: Som fullname: Som, Anup email: som.anup@gmail.com organization: Centre of Bioinformatics, Institute of Interdisciplinary Studies, University of Allahabad, Prayagraj 211002, India |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33862536$$D View this record in MEDLINE/PubMed |
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CitedBy_id | crossref_primary_10_1007_s00441_022_03667_0 crossref_primary_10_3390_antibiotics11070972 crossref_primary_10_1186_s13287_023_03382_9 crossref_primary_10_3390_cancers15235625 crossref_primary_10_1016_j_diff_2023_11_001 crossref_primary_10_1002_advs_202204786 crossref_primary_10_1016_j_compbiolchem_2022_107781 |
Cites_doi | 10.1242/dev.162404 10.1186/1471-2164-10-327 10.1016/j.stem.2014.07.002 10.1016/j.stemcr.2016.02.005 10.1038/ncomms8329 10.1038/srep14722 10.1186/s13059-014-0550-8 10.1093/nar/gkw1138 10.1074/jbc.M113.535799 10.1093/biostatistics/4.2.249 10.1016/j.stem.2017.02.014 10.1093/nar/gkq967 10.1038/emboj.2012.71 10.1103/RevModPhys.74.47 10.1093/bioinformatics/btg405 10.1016/j.yexcr.2020.111924 10.2202/1544-6115.1128 10.1016/j.compbiolchem.2020.107239 10.1016/j.stem.2015.11.007 10.1186/s12864-017-4257-6 10.1038/ncomms15055 10.1016/j.cell.2014.08.029 10.1093/nar/gkv007 10.1016/j.stem.2016.06.011 10.1242/dev.02192 10.1093/nar/gky947 10.1007/s42764-019-00008-4 10.1016/j.stem.2009.05.015 10.1016/j.celrep.2020.02.090 10.1093/jmcb/mjy069 10.1093/bioinformatics/btu170 10.1016/j.celrep.2018.12.099 10.1093/bioinformatics/btt656 10.1186/1471-2105-9-559 10.1038/srep07927 10.1073/pnas.1004584107 10.1038/s41598-018-28173-8 10.1016/j.stem.2016.01.019 10.1002/stem.2507 10.1016/j.stem.2008.03.001 10.1080/15548627.2017.1339001 10.1002/1873-3468.12732 10.1074/jbc.M110.170050 10.1242/dev.146811 10.1038/nrm.2015.28 10.1016/j.celrep.2014.05.037 10.1016/j.cell.2018.01.029 10.1038/ncb2153 10.1038/nrm.2016.8 10.1038/emboj.2013.175 10.1038/nmeth.3317 10.1371/journal.pone.0021800 10.4161/cc.23377 10.1016/j.stem.2013.11.015 10.1093/nar/gkv1351 10.1016/j.stemcr.2019.03.014 10.1074/jbc.274.40.28067 10.1080/10543400903572753 10.1038/ncb2293 10.1016/j.gde.2013.05.002 |
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Snippet | •WGCNA used to identify molecular markers in naive and primed states of human pluripotency.•Naive genes were involved in metabolic processes and primed genes... Pluripotent stem cells (PSCs) have been observed to occur in two distinct states - naive and primed. Both naive and primed state PSCs can give rise to tissues... Pluripotent stem cells (PSCs) have been observed to occur in two distinct states — naive and primed. Both naive and primed state PSCs can give rise to tissues... |
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SubjectTerms | Co-expression network Embryonic stem cell Enrichment analysis Gene module Hub gene Naive and primed pluripotency RNA-Seq Transcription factor |
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Title | Decoding molecular markers and transcriptional circuitry of naive and primed states of human pluripotency |
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