ZBTB12-HERVH-LncRNA axis is a molecular barrier for dedifferentiation of human stem cells
收藏干细胞与再生医学数据中心2022-02-20 更新2024-03-06 收录
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http://data.iscr.ac.cn/Article?id=59014e81ad6118cd8c79a99243e3c447
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Development is generally viewed as one-way traffic of cell state transition from primitive to developmentally advanced states. However, molecular mechanisms that ensure the unidirectional transition remain largely unknown. NanoCAGE sequencing identified an evolutionarily conserved zinc finger repressor, ZBTB12, as a molecular barrier for dedifferentiation of human pluripotent stem cells (hPSCs). Single cell RNA sequencing revealed that ZBTB12 is essential for three germ layer differentiation by blocking hPSC dedifferentiation. Mechanistically, ZBTB12 serves as a master repressor of human endogenous retrovirus H (HERVH). Active HERVH loci drive the expression of overlapping long non-coding RNAs (lncRNAs) whose downregulation by ZBTB12 is necessary for pluripotency exit and lineage derivation. Overall, we have identified a ZBTB12-HERVH-lncRNA axis as molecular machinery that safeguards the unidirectional transition of stem cell fates.
提供机构：
University of California, santa barbara
创建时间：
2022-02-20
