RRC ID 58502
Author Yamauchi K, Ikeda T, Hosokawa M, Nakatsuji N, Kawase E, Chuma S, Hasegawa K, Suemori H.
Title Overexpression of Nuclear Receptor 5A1 Induces and Maintains an Intermediate State of Conversion between Primed and Naive Pluripotency.
Journal Stem Cell Reports
Abstract Naive and primed human pluripotent stem cells (hPSCs) have provided useful insights into the regulation of pluripotency. However, the molecular mechanisms regulating naive conversion remain elusive. Here, we report intermediate naive conversion induced by overexpressing nuclear receptor 5A1 (NR5A1) in hPSCs. The cells displayed some naive features, such as clonogenicity, glycogen synthase kinase 3β, and mitogen-activated protein kinase (MAPK) independence, expression of naive-associated genes, and two activated X chromosomes, but lacked others, such as KLF17 expression, transforming growth factor β independence, and imprinted gene demethylation. Notably, NR5A1 negated MAPK activation by fibroblast growth factor 2, leading to cell-autonomous self-renewal independent of MAPK inhibition. These phenotypes may be associated with naive conversion, and were regulated by a DPPA2/4-dependent pathway that activates the selective expression of naive-associated genes. This study increases our understanding of the mechanisms regulating the conversion from primed to naive pluripotency.
Volume 14(3)
Pages 506-519
Published 2020-3-10
DOI 10.1016/j.stemcr.2020.01.012
PII S2213-6711(20)30033-3
PMID 32084386
PMC PMC7066342
MeSH Gene Expression Regulation / drug effects Glycogen Synthase Kinase 3 / antagonists & inhibitors Glycogen Synthase Kinase 3 / metabolism Histones / metabolism Humans Pluripotent Stem Cells / cytology* Pluripotent Stem Cells / metabolism* Principal Component Analysis Protein Binding / drug effects Protein Kinase Inhibitors / pharmacology Steroidogenic Factor 1 / genetics Steroidogenic Factor 1 / metabolism* Transcription, Genetic / drug effects
IF 6.032
Times Cited 0
DNA material pCMFlag_hsNR5A1 (RDB06299)