A Temporal Chromatin Signature in Human Embryonic Stem Cells Identifies Regulators of Cardiac Development

被引：292

作者：

Paige, Sharon L. ^{[2
,3
,4
]}

Thomas, Sean ^{[10
]}

Stoick-Cooper, Cristi L. ^{[3
,5
,6
]}

Wang, Hao ^{[1
]}

Maves, Lisa ^{[11
]}

Sandstrom, Richard ^{[1
]}

Pabon, Lil ^{[2
,3
,4
]}

Reinecke, Hans ^{[2
,3
,4
]}

Pratt, Gabriel ^{[2
,3
,4
]}

Keller, Gordon ^{[12
]}

Moon, Randall T. ^{[1
,3
]}

Stamatoyannopoulos, John ^{[1
,7
]}

Murry, Charles E. ^{[2
,3
,4
,8
,9
]}

机构：

[1] Univ Washington, Dept Genome Sci, Seattle, WA 98109 USA

[2] Univ Washington, Dept Pathol, Seattle, WA 98109 USA

[3] Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98109 USA

[4] Univ Washington, Ctr Cardiovasc Biol, Seattle, WA 98109 USA

[5] Univ Washington, Dept Pharmacol, Seattle, WA 98109 USA

[6] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98109 USA

[7] Univ Washington, Dept Med, Seattle, WA 98109 USA

[8] Univ Washington, Dept Bioengn, Seattle, WA 98109 USA

[9] Univ Washington, Dept Med Cardiol, Seattle, WA 98109 USA

[10] Gladstone Inst, San Francisco, CA 94158 USA

[11] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA

[12] Ontario Canc Inst, McEwen Ctr Regenerat Med, Toronto, ON M5G 2C4, Canada

来源：

CELL | 2012年 / 151卷 / 01期

关键词：

CARDIOVASCULAR PROGENITOR CELLS; DIRECTED DIFFERENTIATION; PLURIPOTENT; METHYLATION; ZEBRAFISH; POLYCOMB; GENES; EXPRESSION; PROMOTERS; MOUSE;

D O I：

10.1016/j.cell.2012.08.027

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Directed differentiation of human embryonic stem cells(ESCs) into cardiovascular cells provides a model for studying molecular mechanisms of human cardiovascular development. Although it is known that chromatin modification patterns in ESCs differ markedly from those in lineage-committed progenitors and differentiated cells, the temporal dynamics of chromatin alterations during differentiation along a defined lineage have not been studied. We show that differentiation of human ESCs into cardiovascular cells is accompanied by programmed temporal alterations in chromatin structure that distinguish key regulators of cardiovascular development from other genes. We used this temporal chromatin signature to identify regulators of cardiac development, including the homeobox gene MEIS2. Using the zebrafish model, we demonstrate that MEIS2 is critical for proper heart tube formation and subsequent cardiac looping. Temporal chromatin signatures should be broadly applicable to other models of stem cell differentiation to identify regulators and provide key insights into major developmental decisions.

引用

页码：221 / 232

页数：12

共 42 条

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