Derivation of Pre-X Inactivation Human Embryonic Stem Cells under Physiological Oxygen Concentrations

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 counterp...

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Main Authors: Lengner, Christopher J. (Contributor), Gimelbrant, Alexander A. (Author), Erwin, Jennifer A. (Author), Cheng, Albert W. (Contributor), Guenther, Matthew G. (Contributor), Welstead, G. Grant (Contributor), Alagappan, Raaji (Contributor), Frampton, Garrett M. (Contributor), Xu, Ping (Contributor), Muffat, Julien (Contributor), Santagata, Sandro (Contributor), Powers, Doug (Author), Barrett, C. Brent (Author), Young, Richard A. (Contributor), Lee, Jeannie T. (Author), Jaenisch, Rudolf (Contributor), Mitalipova, Maisam (Contributor)
Other Authors: Massachusetts Institute of Technology. Computational and Systems Biology Program (Contributor), Massachusetts Institute of Technology. Department of Biology (Contributor), Whitehead Institute for Biomedical Research (Contributor)
Format: Article
Language:English
Published: Elsevier B.V., 2015-04-03T14:30:42Z.
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Online Access:Get fulltext
LEADER 03032 am a22005413u 4500
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042 |a dc 
100 1 0 |a Lengner, Christopher J.  |e author 
100 1 0 |a Massachusetts Institute of Technology. Computational and Systems Biology Program  |e contributor 
100 1 0 |a Massachusetts Institute of Technology. Department of Biology  |e contributor 
100 1 0 |a Whitehead Institute for Biomedical Research  |e contributor 
100 1 0 |a Lengner, Christopher J.  |e contributor 
100 1 0 |a Cheng, Albert W.  |e contributor 
100 1 0 |a Guenther, Matthew G.  |e contributor 
100 1 0 |a Welstead, G. Grant  |e contributor 
100 1 0 |a Alagappan, Raaji  |e contributor 
100 1 0 |a Frampton, Garrett M.  |e contributor 
100 1 0 |a Xu, Ping  |e contributor 
100 1 0 |a Muffat, Julien  |e contributor 
100 1 0 |a Santagata, Sandro  |e contributor 
100 1 0 |a Young, Richard A.  |e contributor 
100 1 0 |a Jaenisch, Rudolf  |e contributor 
100 1 0 |a Mitalipova, Maisam  |e contributor 
700 1 0 |a Gimelbrant, Alexander A.  |e author 
700 1 0 |a Erwin, Jennifer A.  |e author 
700 1 0 |a Cheng, Albert W.  |e author 
700 1 0 |a Guenther, Matthew G.  |e author 
700 1 0 |a Welstead, G. Grant  |e author 
700 1 0 |a Alagappan, Raaji  |e author 
700 1 0 |a Frampton, Garrett M.  |e author 
700 1 0 |a Xu, Ping  |e author 
700 1 0 |a Muffat, Julien  |e author 
700 1 0 |a Santagata, Sandro  |e author 
700 1 0 |a Powers, Doug  |e author 
700 1 0 |a Barrett, C. Brent  |e author 
700 1 0 |a Young, Richard A.  |e author 
700 1 0 |a Lee, Jeannie T.  |e author 
700 1 0 |a Jaenisch, Rudolf  |e author 
700 1 0 |a Mitalipova, Maisam  |e author 
245 0 0 |a Derivation of Pre-X Inactivation Human Embryonic Stem Cells under Physiological Oxygen Concentrations 
260 |b Elsevier B.V.,   |c 2015-04-03T14:30:42Z. 
856 |z Get fulltext  |u http://hdl.handle.net/1721.1/96368 
520 |a 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. 
520 |a Susan Whitehead 
520 |a Hillel and Liliana Bachrach 
546 |a en_US 
655 7 |a Article 
773 |t Cell