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γH2A.X Modulates Self-renewal and Differentiation of Human Pluripotent Stem Cells. [HuGene-1_0-st]

ABSTRACT: Histone variants are important epigenetic regulators known to play a role in governing the processes of self-renewal and lineage specific differentiation . Phosphorylation of the histone variant H2A.X (γH2A.X) has historically been associated with DNA damage response, but more recent investigations have further demonstrated it’s role in cell cycle, aging and early development. Through both genetic and chemical targeting approaches, we now reveal a direct involvement of γH2A.X in hPSC self-renewal and differentiation decisions in vitro and in vivo. Namely, reduction of γH2A.X levels enhance hPSC differentiation toward mesodermal derivatives with concomitant inhibition of ectodermal derivatives. In contrast, ectopic expression of a constitutively phosphorylated mimic of γH2A.X enhanced hPSCs differentiation toward ectodermal fate while mesodermal differentiation was hindered. These phenotypic observations were associated with γH2A.X occupancy in the promoter regions of key regulatory genes associated with pluripotency and lineage choice. Our study suggests γH2A.X is a functional epigenetic pluripotency marker and novel target for guiding cell-fate commitment during differentiation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE92643 | GEO | 2021/12/06

REPOSITORIES: GEO

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γH2A.X Modulates Self-renewal and Differentiation of Human Pluripotent Stem Cells. [HuGene-2_0-st]

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