Sall4 Regulates Distinct Transcription Circuitries in Different Blastocyst-Derived Stem Cell Lineages

被引：191

作者：

Lim, Chin Yan

Tam, Wai-Leong ^{[1
]}

Zhang, Jinqiu

Ang, Haw Siang ^{[3
]}

Jia, Hui ^{[1
]}

Lipovich, Leonard ^{[1
]}

Ng, Huck-Hui ^{[4
]}

Wei, Chia-Lin ^{[2
]}

Sung, Wing Kin ^{[1
]}

Robson, Paul ^{[4
]}

Yang, Henry ^{[3
]}

Lim, Bing ^{[5
]}

机构：

[1] Genome Inst Singapore, Informat & Math Sci Grp, Singapore 138672, Singapore

[2] Genome Inst Singapore, Genome Technol & Biol Grp, Singapore 138672, Singapore

[3] Bioinformat Inst, Singapore 138671, Singapore

[4] Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore

[5] Harvard Univ, Sch Med, Harvard Inst Med, Boston, MA 02115 USA

来源：

CELL STEM CELL | 2008年 / 3卷 / 05期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/j.stem.2008.08.004

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Stem cells self-renew or differentiate under the governance of a stem-cell-specific transcriptional program, with each transcription factor orchestrating the activities of a particular set of genes. Here we demonstrate that a single transcription factor is able to regulate distinct core circuitries in two different blastocyst-derived stem cell lines, embryonic stem cells (ESCs) and extraembryonic endoderm (XEN) cells. The transcription factor Sall4 is required for early embryonic development and for ESC pluripotency. Sall4 is also expressed in XEN cells, and depletion of Sall4 disrupts self-renewal and induces differentiation. Genome-wide analysis reveals that Sall4 is regulating different gene sets in ESCs and XEN cells, and depletion of Sall4 targets in the respective cell types induces differentiation. With Oct4, Sox2, and Nanog, Sall4 forms a crucial interconnected autoregulatory network in ESCs. In XEN cells, Sall4 regulates the key XEN lineage-associated genes Gata4, Gata6, Sox7, and Sox17. Our findings demonstrate how Sall4 functions as an essential sternness factor for two different stem cell lines.

引用

页码：543 / 554

页数：12

共 42 条

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