The role of ESRG in human pluripotency
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PROVIDER: PRJNA659235 | ENA |
REPOSITORIES: ENA
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Project description:Human pluripotent stem cells (PSCs) express human endogenous retroviruses type-H (HERV-Hs), which exist more than a thousand copies on the human genome and frequently produce chimeric transcripts as long-non-coding RNAs (lncRNAs) fused with downstream neighbor genes. Previous studies showed that HERV-H expression is required for the maintenance of PSC identity, and the aberrant HERV-H expression attenuated neural differentiation potentials, but little is known what their roles are. In this study, therefore, we focused on ESRG, which is known as a PSC-related HERV-H-driven lncRNA. The global transcriptome data of various tissues and cell lines and quantitative expression analysis showed that ESRG expression is much higher than other HERV-Hs and tightly silenced after differentiation, letting us hypothesize its crucial role in human pluripotency. However, the loss of function by the complete excision of the entire ESRG gene body using a CRISPR/Cas9 platform revealed that ESRG is dispensable for the maintenance of primed and naïve pluripotent states. The loss of ESRG hardly affects the global gene expression of PSCs and differentiation potentials toward trilineage. Differentiated cells derived from ESRG knockout PSCs retained the potential to be reprogrammed into induced PSC (iPSC) by the forced expression of OCT3/4, SOX2, and KLF4. In conclusion, ESRG is dispensable for the maintenance and the recapturing of human pluripotency.
2021-05-11 | GSE156834 | GEO
Project description:Human pluripotent stem cells (PSCs) express human endogenous retroviruses type-H (HERV-Hs), which exist more than a thousand copies on the human genome and frequently produce chimeric transcripts as long-non-coding RNAs (lncRNAs) fused with downstream neighbor genes. Previous studies showed that HERV-H expression is required for the maintenance of PSC identity, and the aberrant HERV-H expression attenuated neural differentiation potentials, but little is known what their roles are. In this study, therefore, we focused on ESRG, which is known as a PSC-related HERV-H-driven lncRNA. The global transcriptome data of various tissues and cell lines and quantitative expression analysis showed that ESRG expression is much higher than other HERV-Hs and tightly silenced after differentiation, letting us hypothesize its crucial role in human pluripotency. However, the loss of function by the complete excision of the entire ESRG gene body using a CRISPR/Cas9 platform revealed that ESRG is dispensable for the maintenance of primed and naïve pluripotent states. The loss of ESRG hardly affects the global gene expression of PSCs and differentiation potentials toward trilineage. Differentiated cells derived from ESRG knockout PSCs retained the potential to be reprogrammed into induced PSC (iPSC) by the forced expression of OCT3/4, SOX2, and KLF4. In conclusion, ESRG is dispensable for the maintenance and the recapturing of human pluripotency.
2021-05-11 | GSE159101 | GEO
Project description:Human pluripotent stem cells (PSCs) express human endogenous retroviruses type-H (HERV-Hs), which exist more than a thousand copies on the human genome and frequently produce chimeric transcripts as long-non-coding RNAs (lncRNAs) fused with downstream neighbor genes. Previous studies showed that HERV-H expression is required for the maintenance of PSC identity, and the aberrant HERV-H expression attenuated neural differentiation potentials, but little is known what their roles are. In this study, therefore, we focused on ESRG, which is known as a PSC-related HERV-H-driven lncRNA. The global transcriptome data of various tissues and cell lines and quantitative expression analysis showed that ESRG expression is much higher than other HERV-Hs and tightly silenced after differentiation, letting us hypothesize its crucial role in human pluripotency. However, the loss of function by the complete excision of the entire ESRG gene body using a CRISPR/Cas9 platform revealed that ESRG is dispensable for the maintenance of primed and naïve pluripotent states. The loss of ESRG hardly affects the global gene expression of PSCs and differentiation potentials toward trilineage. Differentiated cells derived from ESRG knockout PSCs retained the potential to be reprogrammed into induced PSC (iPSC) by the forced expression of OCT3/4, SOX2, and KLF4. In conclusion, ESRG is dispensable for the maintenance and the recapturing of human pluripotency.
2021-05-11 | GSE171849 | GEO
Project description:Human pluripotent stem cells (PSCs) express human endogenous retroviruses type-H (HERV-Hs), which exist more than a thousand copies on the human genome and frequently produce chimeric transcripts as long-non-coding RNAs (lncRNAs) fused with downstream neighbor genes. Previous studies showed that HERV-H expression is required for the maintenance of PSC identity, and the aberrant HERV-H expression attenuated neural differentiation potentials, but little is known what their roles are. In this study, therefore, we focused on ESRG, which is known as a PSC-related HERV-H-driven lncRNA. The global transcriptome data of various tissues and cell lines and quantitative expression analysis showed that ESRG expression is much higher than other HERV-Hs and tightly silenced after differentiation, letting us hypothesize its crucial role in human pluripotency. However, the loss of function by the complete excision of the entire ESRG gene body using a CRISPR/Cas9 platform revealed that ESRG is dispensable for the maintenance of primed and naïve pluripotent states. The loss of ESRG hardly affects the global gene expression of PSCs and differentiation potentials toward trilineage. Differentiated cells derived from ESRG knockout PSCs retained the potential to be reprogrammed into induced PSC (iPSC) by the forced expression of OCT3/4, SOX2, and KLF4. In conclusion, ESRG is dispensable for the maintenance and the recapturing of human pluripotency.
2021-05-11 | GSE171627 | GEO
Project description:The role of ESRG in human pluripotency III
| PRJNA720332 | ENA
Project description:The role of ESRG in human pluripotency II
| PRJNA667693 | ENA
Project description:The role of ESRG in human pluripotency IV
| PRJNA721196 | ENA
Project description:Elucidating the mechanism of self-renewal and pluripotency maintenance of human embryonic stem cells (hESCs) is of great significance in basic research and clinical applications. Long non-coding RNAs (lncRNAs) have been shown to play a key role in the self-renewal and pluripotency maintenance of hESCs. We previously reported that the lncRNA ESRG, which is highly expressed in undifferentiated hESCs, can interact with the replication licensing factor MCM2 and inhibit the p53 pathway to maintain the self-renewal and pluripotency of hPSCs. In addition to MCM2, RNA pull-down mass spectrometry showed that ESRG could also bind to other proteins, among which heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) attracted our attention. In this study, we show that HNRNPA1 can maintain self-renewal and pluripotency of hESCs. ESRG binds to and stabilizes HNRNPA1 protein through the ubiquitin-proteasome pathway. In addition, knockdown of ESRG or HNRNPA1 resulted in alternative splicing of TCF3, which originally and primarily encodes E12, to mainly encode E47 and inhibit CDH1 expression. HNRNPA1 could rescue the biological function changes of hESCs caused by ESRG knockdown or overexpression. Our results suggest that ESRG regulates the alternative splicing of TCF3 to affect CDH1 expression and maintain hESCs self-renewal and pluripotency by binding and stabilizing HNRNPA1 protein. This study lays a good foundation for exploring the new molecular regulatory mechanism by which ESRG maintains hESCs self-renewal and pluripotency.
2024-03-05 | GSE236745 | GEO
Project description:Long non-coding RNA ESRG was first identified in our previous study, but its physiological function, regulatory and action mechanisms in human pluripotent stem cells (hPSCs) remain largely unexplored. Here, we found that ESRG is specifically and highly expressed in hPSCs, and its transcription is directly regulated by OCT4, suggesting that ESRG may be an integral component of the core regulatory circuit regulating the pluripotent state of hPSCs. Knockdown of ESRG induces hPSC differentiation, cell cycle arrest, and apoptosis. Mechanistically, ESRG binds to minichromosome maintenance protein 2 (MCM2), a replication-licensing factor, to sustain its steady-state level and nuclear translocation, safeguarding error-free DNA replication. Further study showed that inhibition of the interaction bewteen ESRG and MCM2 results in DNA damage and activation of p53 signaling pathway, ultimately deregulates deregulates pluripotency and self-renewal of hPSCs. In sum, our observations suggest that ESRG, as a novel target of OCT4, plays an essential role in maintaining the pluripotency and self-renewal of hPSCs in collaboration with MCM2 to suppress p53 signaling. These findings provide critical insights into the mechanisms underlying the maintenance of self-renewal and pluripotency in hPSCs.
2023-03-02 | GSE190957 | GEO
Project description:ESRG regulates alternative splicing of TCF3 to maintain hESCs self-renewal and pluripotency
| PRJNA992127 | ENA