In Vitro Derivation of Quiescent Mouse Embryonic Stem Cells Based on Distinct Mitochondrial Activity

Khoa, Le Tran Phuc; Dou, Yali

doi:10.1016/j.xpro.2020.100136

Cited by 1 publication

(2 citation statements)

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“…The spontaneous qESCs can be isolated by live-cell sorting after staining with the lipophilic cationic dye Tetramethylrhodamine Methyl Ester (TMRM) 5 , 15 (Supplementary Fig. 1 ), which measures the MMP across the inner mitochondrial membrane.…”

Section: Resultsmentioning

confidence: 99%

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Quiescence enables unrestricted cell fate in naive embryonic stem cells

Khoa,

Yang,

Shan

et al. 2024

Nat Commun

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Quiescence in stem cells is traditionally considered as a state of inactive dormancy or with poised potential. Naive mouse embryonic stem cells (ESCs) can enter quiescence spontaneously or upon inhibition of MYC or fatty acid oxidation, mimicking embryonic diapause in vivo. The molecular underpinning and developmental potential of quiescent ESCs (qESCs) are relatively unexplored. Here we show that qESCs possess an expanded or unrestricted cell fate, capable of generating both embryonic and extraembryonic cell types (e.g., trophoblast stem cells). These cells have a divergent metabolic landscape comparing to the cycling ESCs, with a notable decrease of the one-carbon metabolite S-adenosylmethionine. The metabolic changes are accompanied by a global reduction of H3K27me3, an increase of chromatin accessibility, as well as the de-repression of endogenous retrovirus MERVL and trophoblast master regulators. Depletion of methionine adenosyltransferase Mat2a or deletion of Eed in the polycomb repressive complex 2 results in removal of the developmental constraints towards the extraembryonic lineages. Our findings suggest that quiescent ESCs are not dormant but rather undergo an active transition towards an unrestricted cell fate.

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Section: Resultsmentioning

confidence: 99%

“…Fractionation of ESCs with high and low ΔΨ m levels was performed as previously described 5 , 15 . 25 nM of TMRM (Thermo Fisher Scientific, #T668), was used for staining.…”

Section: Methodsmentioning

confidence: 99%