Derivation of pre-X inactivation human embryonic stem cells under physiological oxygen concentrations
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ABSTRACT: The presence of two active X chromosomes (XaXa) is a hallmark of the ground state of pluripotency specific to murine embryonic stem cells (ESCs). Human ESCs invariably exhibit signs of X chromosome inactivation (XCI) and are considered developmentally more advanced than their murine counterparts. We describe the establishment of the first XaXa hESCs derived under physiological oxygen concentrations. Using these cell lines we demonstrate that (1) differentiation of hESCs induces random XCI in a manner similar to murine ESCs, (2) exposure to atmospheric oxygen is sufficient to induce irreversible XCI and dramatic changes throughout the transcriptome, (3) the Xa exhibits heavy methylation of the XIST promoter region, and (4) XCI is associated with demethylation and transcriptional activation of XIST along with H3K27-me3 deposition across the Xi. These findings suggest that XaXa cells exist in the ICM of the human blastocyst and that this state is preserved in vitro through culture under physiological oxygen. Gene expression profiling was performed on human ES cell lines isolated and maintained under different oxygen concentrations
ORGANISM(S): Homo sapiens
SUBMITTER: Dong Powers
PROVIDER: E-GEOD-20937 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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