We are seeing patients in-person and through Video Visits. Learn more about how we’re keeping you safe and please review our updated visitor policy. Please also consider supporting Weill Cornell Medicine’s efforts to support our front-line workers.

Lipid Deprivation Induces a Stable, Naive-to-Primed Intermediate State of Pluripotency in Human PSCs.

TitleLipid Deprivation Induces a Stable, Naive-to-Primed Intermediate State of Pluripotency in Human PSCs.
Publication TypeJournal Article
Year of Publication2019
AuthorsCornacchia D, Zhang C, Zimmer B, Chung SYoung, Fan Y, Soliman MA, Tchieu J, Chambers SM, Shah H, Paull D, Konrad C, Vincendeau M, Noggle SA, Manfredi G, Finley LWS, Cross JR, Betel D, Studer L
JournalCell Stem Cell
Date Published2019 May 21
ISSN1875-9777
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 epigenomic features despite providing primed-state-sustaining growth factor conditions. Transcriptionally, E8 hPSCs are marked by activated lipid biosynthesis and suppressed MAPK/TGF-β 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.

DOI10.1016/j.stem.2019.05.001
Alternate JournalCell Stem Cell
PubMed ID31155483