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Learn MoreHuman nave pluripotency state cells can be derived from direct isolation of inner cell mass or primed-to-nave resetting of human embryonic stem cells (hESCs) through different combinations of transcription factors, small molecular inhibitors and growth factors. Long noncoding RNAs (lncRNAs) have been identified to be crucial in diverse biological processes, including pluripotency regulatory circuit of mouse pluripotent stem cells (PSCs), but few are involved in human PSCs regulation of pluripotency and nave pluripotency derivation. This study initially planned to discover more lncRNAs possibly playing significant roles in the regulation of human PSCs pluripotency, but accidently identified a lncRNA whose knockdown in human PSCs induced nave-like pluripotency conversion. The results indicated that knockdown of CCDC144NL-AS1 induces nave-like state conversion of human PSCs in the absence of additional transcription factors or small molecular inhibitors. CCDC144NL-AS1-KD human PSCs reveal nave-like pluripotency features, such as elevated expression of nave pluripotency associated genes, increased developmental capacity, analogous transcriptional profiles to human nave PSCs, and global reduction of repressive chromatin modification marks. Furthermore, CCDC144NL-AS1-KD human PSCs display inhibition of MAPK (ERK), accumulation of active -catenin, and upregulation of some LIF/STAT3 target genes, and all of these are concordant with previous reported traits of human nave PSCs. SOURCE: Kunshan Zhang (mart555@163.com) - Tongji Hospital, Tongji University
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