Gata4 directs development of cardiac-inducing endoderm from ES cells.
Gata4 directs development of cardiac-inducing endoderm from ES cells.
复制标题
DOI：
10.1016/j.ydbio.2009.10.003
复制
发表时间：
2010-01-01
影响因子：
2.7
通讯作者：
Evans, Todd
中科院分区：
文献类型：
--
作者：
Holtzinger, Audrey;Rosenfeld, Gabriel E.;Evans, Todd
转录因子Gata4是正常心脏形态发生所必需的，调节心肌细胞的存活、生长和增殖。我们通过开发一种在胚胎干细胞中有条件地表达Gata4的系统，测试了Gata4是否可以从未确定的干细胞或祖细胞群体中指定心肌细胞的命运。我们发现，在含有这些细胞的类胚体培养中，GATA4的表达足以通过非细胞自主机制显著促进心肌细胞的生成。表达Gata4的细胞不产生心脏或其他中胚层衍生物。相反，Gata4的表达指导着两种Sox17+内胚层的发育。这包括内脏内胚层的EpCAM+DPP4+亚型。此外，GATA4产生类似数量的EPCAM+DPP4−最终内胚层，富含CXCR4、FoxA2、FoxA3、Dlx5和其他特征转录本。这两种类型的内胚层都表达心脏诱导因子，包括WNT拮抗剂Dkk1和Sfrp5，尽管内脏内胚层亚型具有更高的心脏诱导活性，这与编码BMPs的转录本水平相对增强有关。即使在通常支持中胚层发育的条件下，表达Gata4的细胞最终也会表达分化标记，表明对肝脏发育的承诺。结果表明，Gata4能够指定内胚层的命运，从而促进相关的中胚层产生心肌祖细胞，具有时间和空间特异性。
The transcription factor Gata4 is essential for normal heart morphogenesis and regulates the survival, growth, and proliferation of cardiomyocytes. We tested if Gata4 can specify cardiomyocyte fate from an uncommitted stem or progenitor cell population, by developing a system for conditional expression of Gata4 in embryonic stem cells. We find that in embryoid body cultures containing even a low ratio of these cells, expression of Gata4 is sufficient to enhance significantly the generation of cardiomyocytes, via a non-cell-autonomous mechanism. The Gata4-expressing cells do not generate cardiac or other mesoderm derivatives. Rather, Gata4 expression directs the development of two types of Sox17+ endoderm. This includes an epCam+Dpp4+ subtype of visceral endoderm. In addition, Gata4 generates similar amounts of epCam+Dpp4− definitive endoderm enriched for Cxcr4, FoxA2, FoxA3, Dlx5 and other characteristic transcripts. Both types of endoderm express cardiac-inducing factors, including WNT antagonists Dkk1 and Sfrp5, although the visceral endoderm subtype has much higher cardiac inducing activity correlating with relatively enhanced levels of transcripts encoding BMPs. The Gata4-expressing cells eventually express differentiation markers showing commitment to liver development, even under conditions that normally support mesoderm development. The results suggest that Gata4 is capable of specifying endoderm fates that facilitate, with temporal and spatial specificity, the generation of cardiomyocyte progenitors from associated mesoderm.
登录
查看更多内容
影响因子：
3.9
作者：
Bin, Zeng;Sheng, Lin-Guo;Hui, Shen
通讯作者：
Hui, Shen
影响因子：
1.2
作者：
Finley, KR;Tennessen, J;Shawlot, W
通讯作者：
Shawlot, W
DOI：
10.1073/pnas.0602543103
发表时间：
2006-09-26
影响因子：
11.1
作者：
Bisping, Egbert;Ikeda, Sadakatsu;Pu, William T.
通讯作者：
Pu, William T.
影响因子：
10.5
作者：
Kuo, CT;Morrisey, EE;Leiden, JM
通讯作者：
Leiden, JM
影响因子：
9.3
作者：
Kattman, Steven J.;Adler, Eric D.;Keller, Gordon M.
通讯作者：
Keller, Gordon M.