Derivation of Pre-X Inactivation Human Embryonic Stem Cells under Physiological Oxygen Concentrations
Author(s)Lengner, Christopher J.; Gimelbrant, Alexander A.; Erwin, Jennifer A.; Cheng, Albert W.; Guenther, Matthew G.; Welstead, G. Grant; Alagappan, Raaji; Frampton, Garrett M.; Xu, Ping; Muffat, Julien; Santagata, Sandro; Powers, Doug; Barrett, C. Brent; Young, Richard A.; Lee, Jeannie T.; Jaenisch, Rudolf; Mitalipova, Maisam; ... Show more Show less
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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 (hESCs) invariably exhibit signs of X chromosome inactivation (XCI) and are considered developmentally more advanced than their murine counterparts. We describe the establishment of 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) chronic exposure to atmospheric oxygen is sufficient to induce irreversible XCI with minor changes of 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 indicate that the human blastocyst contains pre-X-inactivation cells and that this state is preserved in vitro through culture under physiological oxygen.
DepartmentMassachusetts Institute of Technology. Computational and Systems Biology Program; Massachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research
Lengner, Christopher J., Alexander A. Gimelbrant, Jennifer A. Erwin, Albert Wu Cheng, Matthew G. Guenther, G. Grant Welstead, Raaji Alagappan, et al. “Derivation of Pre-X Inactivation Human Embryonic Stem Cells Under Physiological Oxygen Concentrations.” Cell 141, no. 5 (May 2010): 872–883. © 2010 Elsevier Inc.
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