ESRG is critical to maintain the cell survival and self-renewal/pluripotency of hPSCs by collaborating with MCM2 to suppress p53 pathway

Abstract

The mechanisms of self-renewal and pluripotency maintenance of human pluripotent stem cells (hPSCs) have not been fully elucidated, especially for the role of those poorly characterized long noncoding RNAs (lncRNAs). ESRG is a lncRNA highly expressed in hPSCs, and its functional roles are being extensively explored in the field. Here, we identified that the transcription of ESRG can be directly regulated by OCT4, a key self-renewal factor in hPSCs. Knockdown of ESRG induces hPSC differentiation, cell cycle arrest, and apoptosis. ESRG binds to MCM2, a replication-licensing factor, to sustain its steady-state level and nuclear location, safeguarding error-free DNA replication. Further study showed that ESRG knockdown leads to MCM2 abnormalities, resulting in DNA damage and activation of the p53 pathway, ultimately impairs hPSC self-renewal and pluripotency, and induces cell apoptosis. In summary, our study suggests that ESRG , as a novel target of OCT4, plays an essential role in maintaining the cell survival and self-renewal/pluripotency 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 by lncRNAs.

KNTC1 knockdown inhibits the proliferation and migration of osteosarcoma cells by MCM2

“…MCM2 was a member of the protein microchromosome maintenance family and was involved in the regulation of DNA replication and cell cycle 28 . Abnormal expression of MCM2 not only regulated the cycle process and proliferation of cerebral microvascular endothelial cells, 29 but also participated in the self‐renewal and pluripotent maintenance of human pluripotent stem cells 30 . Besides, as a proliferative marker, MCM2 was significantly overexpressed in almost all cancers, which was associated with tumor staging in multiple cancers, and played a carcinogenic role 31 .…”

“…28 Abnormal expression of MCM2 not only regulated the cycle process and proliferation of cerebral microvascular endothelial cells, 29 but also participated in the self-renewal and pluripotent maintenance of human pluripotent stem cells. 30 Besides, as a proliferative marker, MCM2 was significantly overexpressed in almost all cancers, which was associated with tumor staging in multiple cancers, and played a carcinogenic role. 31 Zhou et al found that MCM2 was highly expressed in sarcoma and was a prognostic biomarker for human sarcoma, 32 which was consistent with our study.…”

Construction of functional neural network tissue combining CBD-NT3-modified linear-ordered collagen scaffold and TrkC-modified iPSC-derived neural stem cells for spinal cord injury repair

“…iPSCs were passaged every 4–5 days using EDTA dissociation buffer (Gibco, USA). The dispersed cells were collected, aspirated in npEpic medium, and replated at a 1:4–1:6 ratio [ 25 ].…”