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

被引：301

作者：

Lengner, Christopher J. ^{[1
]}

Gimelbrant, Alexander A. ^{[4
,5
]}

Erwin, Jennifer A. ^{[6
,7
,8
]}

Cheng, Albert Wu ^{[1
,3
]}

Guenther, Matthew G. ^{[1
]}

Welstead, G. Grant ^{[1
]}

Alagappan, Raaji ^{[1
]}

Frampton, Garrett M. ^{[1
,2
]}

Xu, Ping ^{[1
]}

Muffat, Julien ^{[1
]}

Santagata, Sandro ^{[1
]}

Powers, Doug ^{[9
]}

Barrett, C. Brent ^{[10
]}

Young, Richard A. ^{[1
,2
]}

Lee, Jeannie T. ^{[6
,7
,8
]}

Jaenisch, Rudolf ^{[1
,2
]}

Mitalipova, Maisam ^{[1
]}

机构：

[1] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[2] MIT, Dept Biol, Cambridge, MA 02139 USA

[3] MIT, Dept Computat & Syst Biol, Cambridge, MA 02139 USA

[4] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA

[5] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA

[6] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA

[7] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA

[8] Howard Hughes Med Inst, Ann Arbor, MI 48108 USA

[9] Incept Biosyst, Ann Arbor, MI 48108 USA

[10] Waltham Ctr, Boston IVF, Waltham, MA 02451 USA

来源：

CELL | 2010年 / 141卷 / 05期

关键词：

EARLY MOUSE EMBRYOS; CHROMOSOME INACTIVATION; IN-VITRO; HUMAN BLASTOCYSTS; HISTONE H3; XIST RNA; SELF-RENEWAL; LINES; DIFFERENTIATION; METHYLATION;

D O I：

10.1016/j.cell.2010.04.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：872 / 883

页数：12

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