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Eomesodermin 在没有激活素的情况下诱导胚胎干细胞表达 Mesp1 并进行心脏分化。

Eomesodermin induces Mesp1 expression and cardiac differentiation from embryonic stem cells in the absence of Activin.

机构信息

IRIBHM (Institute for Interdisciplinary Research), Université Libre de Bruxelles, Campus Erasme, Brussels B-1070, Belgium.

出版信息

EMBO Rep. 2012 Apr;13(4):355-62. doi: 10.1038/embor.2012.23.

DOI:10.1038/embor.2012.23
PMID:22402664
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3321156/
Abstract

The transcription factor Eomesodermin (Eomes) is involved in early embryonic patterning, but the range of cell fates that it controls as well as its mechanisms of action remain unclear. Here we show that transient expression of Eomes promotes cardiovascular fate during embryonic stem cell differentiation. Eomes also rapidly induces the expression of Mesp1, a key regulator of cardiovascular differentiation, and directly binds to regulatory sequences of Mesp1. Eomes effects are strikingly modulated by Activin signalling: high levels of Activin inhibit the promotion of cardiac mesoderm by Eomes, while they enhance Eomes-dependent endodermal specification. These results place Eomes upstream of the Mesp1-dependent programme of cardiogenesis, and at the intersection of mesodermal and endodermal specification, depending on the levels of Activin/Nodal signalling.

摘要

转录因子 Eomesodermin (Eomes) 参与早期胚胎模式形成，但它控制的细胞命运范围及其作用机制仍不清楚。在这里，我们表明 Eomes 的瞬时表达在胚胎干细胞分化过程中促进了心血管命运。Eomes 还迅速诱导了心血管分化的关键调节因子 Mesp1 的表达，并直接结合到 Mesp1 的调节序列上。Eomes 的作用受激活素信号的显著调节：高水平的激活素抑制 Eomes 对心脏中胚层的促进作用，而同时增强 Eomes 依赖的内胚层特化作用。这些结果将 Eomes 置于依赖 Mesp1 的心脏发生程序的上游，并根据激活素/Nodal 信号的水平处于中胚层和内胚层特化的交汇处。

相似文献

[1]
Eomesodermin induces Mesp1 expression and cardiac differentiation from embryonic stem cells in the absence of Activin.

EMBO Rep. 2012-4

[2]
The T-box transcription factor Eomesodermin acts upstream of Mesp1 to specify cardiac mesoderm during mouse gastrulation.

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[3]
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[4]
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[5]
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J Mol Cell Biol. 2014-8

[6]
The histone demethylase Jmjd3 sequentially associates with the transcription factors Tbx3 and Eomes to drive endoderm differentiation.

EMBO J. 2013-4-12

[7]
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J Biol Chem. 2009-1-23

[8]
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[9]
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[10]
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[7]
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本文引用的文献

[1]
Inducible cassette exchange: a rapid and efficient system enabling conditional gene expression in embryonic stem and primary cells.

Stem Cells. 2011-10

[2]
The T-box transcription factor Eomesodermin acts upstream of Mesp1 to specify cardiac mesoderm during mouse gastrulation.

Nat Cell Biol. 2011-8-7

[3]
Induction of MesP1 by Brachyury(T) generates the common multipotent cardiovascular stem cell.

Cardiovasc Res. 2011-6-1

[4]
Defining the earliest step of cardiovascular progenitor specification during embryonic stem cell differentiation.

J Cell Biol. 2011-3-7

[5]
Generation of anterior foregut endoderm from human embryonic and induced pluripotent stem cells.

Nat Biotechnol. 2011-2-27

[6]
Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines.

Cell Stem Cell. 2011-2-4

[7]
Pluripotency factors regulate definitive endoderm specification through eomesodermin.

Genes Dev. 2011-1-18

[8]
Mesp1: a key regulator of cardiovascular lineage commitment.

Circ Res. 2010-12-10

[9]
Mechanisms of neural specification from embryonic stem cells.

Curr Opin Neurobiol. 2010-1-14

[10]
Tgif1 and Tgif2 regulate Nodal signaling and are required for gastrulation.

Development. 2010-1

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