Transcriptional and Epigenetic Dynamics during Specification of Human Embryonic Stem Cells

被引：338

作者：

Gifford, Casey A. ^{[1
,2
,3
]}

Ziller, Michael J. ^{[1
,2
,3
]}

Gu, Hongcang ^{[1
]}

Trapnell, Cole ^{[1
,3
]}

Donaghey, Julie ^{[1
,2
,3
]}

Tsankov, Alexander ^{[1
,2
,3
]}

Shalek, Alex K. ^{[4
]}

Kelley, David R. ^{[1
,3
]}

Shishkin, Alexander A. ^{[1
]}

Issner, Robbyn ^{[1
]}

Zhang, Xiaolan ^{[1
]}

Coyne, Michael ^{[1
]}

Fostel, Jennifer L. ^{[1
]}

Holmes, Laurie ^{[1
]}

Meldrim, Jim ^{[1
]}

Guttman, Mitchell ^{[1
]}

Epstein, Charles ^{[1
]}

Park, Hongkun ^{[4
]}

Kohlbacher, Oliver ^{[5
,6
]}

Rinn, John ^{[1
,3
,7
]}

Gnirke, Andreas ^{[1
]}

Lander, Eric S. ^{[1
,8
]}

Bernstein, Bradley E. ^{[1
,9
,10
,11
]}

Meissner, Alexander ^{[1
,2
,3
]}

机构：

[1] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[2] Harvard Stem Cell Inst, Cambridge, MA 02138 USA

[3] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[4] Harvard Univ, Dept Chem, Cambridge, MA 02138 USA

[5] Univ Tubingen, Ctr Bioinformat, D-72076 Tubingen, Germany

[6] Univ Tubingen, Quantitat Biol Ctr, D-72076 Tubingen, Germany

[7] Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA

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

[9] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA

[10] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[11] Harvard Univ, Sch Med, Boston, MA 02114 USA

来源：

CELL | 2013年 / 153卷 / 05期

基金：

美国国家卫生研究院;

关键词：

DNA METHYLATION; MAMMALIAN DEVELOPMENT; HISTONE MODIFICATIONS; REGULATORY REGIONS; HUMAN ES; DIFFERENTIATION; CHROMATIN; EXPRESSION; GENERATION; ENHANCERS;

D O I：

10.1016/j.cell.2013.04.037

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：

Differentiation of human embryonic stem cells (hESCs) provides a unique opportunity to study the regulatory mechanisms that facilitate cellular transitions in a human context. To that end, we performed comprehensive transcriptional and epigenetic profiling of populations derived through directed differentiation of hESCs representing each of the three embryonic germ layers. Integration of whole-genome bisulfite sequencing, chromatin immunoprecipitation sequencing, and RNA sequencing reveals unique events associated with specification toward each lineage. Lineage-specific dynamic alterations in DNA methylation and H3K4me1 are evident at putative distal regulatory elements that are frequently bound by pluripotency factors in the undifferentiated hESCs. In addition, we identified germ-layer-specific H3K27me3 enrichment at sites exhibiting high DNA methylation in the undifferentiated state. A better understanding of these initial specification events will facilitate identification of deficiencies in current approaches, leading to more faithful differentiation strategies as well as providing insights into the rewiring of human regulatory programs during cellular transitions.

引用

页码：1149 / 1163

页数：15

共 48 条

[1] Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells [J].