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ESRG, a novel target of OCT4, maintains self-renewal and pluripotency of human pluripotent stem cells in collaboration with MCM2

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE190957 | GEO | 2023/03/02

REPOSITORIES: GEO

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ESRG regulates alternative splicing of TCF3 to maintain hESCs self-renewal and pluripotency

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