Lipid deprivation induces a stable, naive-to-primed intermediate state of pluripotency in human PSCs Journal Article

   

Authors:	Cornacchia, D.; Zhang, C.; Zimmer, B.; Chung, S. Y.; Fan, Y.; Soliman, M. A.; Tchieu, J.; Chambers, S. M.; Shah, H.; Paull, D.; Konrad, C.; Vincendeau, M.; Noggle, S. A.; Manfredi, G.; Finley, L. W. S.; Cross, J. R.; Betel, D.; Studer, L.
Article Title:	Lipid deprivation induces a stable, naive-to-primed intermediate state of pluripotency in human PSCs
Abstract:	Current challenges in capturing naive human pluripotent stem cells (hPSCs) suggest that the factors regulating human naive versus primed pluripotency remain incompletely defined. Here we demonstrate that the widely used Essential 8 minimal medium (E8) captures hPSCs at a naive-to-primed intermediate state of pluripotency expressing several naive-like developmental, bioenergetic, and epige-nomic features despite providing primed-statesustaining growth factor conditions. Transcriptionally, E8 hPSCs are marked by activated lipid biosynthesis and suppressed MAPK/TGF-beta gene expression, resulting in endogenous ERK inhibition. These features are dependent on lipid-free culture conditions and are lost upon lipid exposure, whereas short-term pharmacological ERK inhibition restores naive-to-primed intermediate traits even in the presence of lipids. Finally, we identify de novo lipogenesis as a common transcriptional signature of E8 hPSCs and the pre-implantation human epiblast in vivo. These findings implicate exogenous lipid availability in regulating human pluripotency and define E8 hPSCs as a stable, naive-to-primed intermediate (NPI) pluripotent state.
Keywords:	methylation; differentiation; embryonic stem-cells; fatty-acids; derivation; culture; human es; energy-metabolism; ground-state; acetyl-coa
Journal Title:	Cell Stem Cell
Volume:	25
Issue:	1
ISSN:	1934-5909
Publisher:	Cell Press
Date Published:	2019-07-03
Start Page:	120
End Page:	136.e10
Language:	English
ACCESSION:	WOS:000473770700012
DOI:	10.1016/j.stem.2019.05.001
PROVIDER:	wos
PUBMED:	31155483
PMCID:	PMC7549840
Notes:	Article -- Source: Wos

https://synapse.mskcc.org/synapse/works/has_related_data_chk/150435