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Putting Stem Cells on a Low-Fat Diet Switches Their Pluripotent State
- Source :
- Cell Stem Cell
- Publication Year :
- 2019
-
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.
- Subjects :
- Pluripotent Stem Cells
Cellular differentiation
Cell
Biology
Article
03 medical and health sciences
0302 clinical medicine
Genetics
medicine
Humans
Epigenetics
Induced pluripotent stem cell
Diet, Fat-Restricted
Embryonic Stem Cells
030304 developmental biology
0303 health sciences
Cell Differentiation
Cell Biology
Low fat diet
Embryonic stem cell
Lipids
Cell biology
medicine.anatomical_structure
Molecular Medicine
Stem cell
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 18759777
- Volume :
- 25
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cell stem cell
- Accession number :
- edsair.doi.dedup.....aa2cecc9f7cd8c6e41f7755745cf9347