Mesp1 acts as a master regulator of multipotent cardiovascular progenitor specification
Mesp1 acts as a master regulator of multipotent cardiovascular progenitor specification
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DOI：
10.1016/j.stem.2008.06.009
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发表时间：
2008-07-01
期刊：
影响因子：
23.9
通讯作者：
Blanpain, Cedric
中科院分区：
文献类型：
--
作者：
Bondue, Antoine;Lapouge, Gaelle;Blanpain, Cedric
在胚胎发育过程中，多能心血管祖细胞是从早期中胚层分化而来的。使用小鼠胚胎干细胞中的基因表达可以暂时调节，我们已经发现，瞬时表达的Mesp1显着加速和增强多能心血管祖细胞规格通过内在和细胞自主机制。全基因组转录分析表明，Mesp1快速激活和抑制一组离散的基因，染色质免疫沉淀显示，Mesp1直接结合到位于心脏核心转录机制中许多关键基因启动子的调控DNA序列，导致其快速上调。Mesp1还直接抑制调节其他早期中胚层和内胚层细胞命运的关键基因的表达。我们的研究结果表明，Mesp1作为一个关键的调节开关在心血管规范，居住在负责心血管细胞命运决定的基因网络的层次结构的顶部。
During embryonic development, multipotent cardiovascular progenitor cells are specified from early mesoderm. Using mouse ESCs in which gene expression can be temporally regulated, we have found that transient expression of Mesp1 dramatically accelerates and enhances multipotent cardiovascular progenitor specification through an intrinsic and cell autonomous mechanism. Genome-wide transcriptional analysis indicates that Mesp1 rapidly activates and represses a discrete set of genes, and chromatin immunoprecipitation shows that Mesp1 directly binds to regulatory DNA sequences located in the promoter of many key genes in the core cardiac transcriptional machinery, resulting in their rapid up-regulation. Mesp1 also directly represses the expression of key genes regulating other early mesoderm and endoderm cell fates. Our results demonstrate that Mesp1 acts as a key regulatory switch during cardiovascular specification, residing at the top of the hierarchy of the gene network responsible for cardiovascular cell-fate determination.