Endocardium differentiation through Sox17 expression in endocardium precursor cells regulates heart development in mice
Endocardium differentiation through Sox17 expression in endocardium precursor cells regulates heart development in mice
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DOI：
10.1038/s41598-019-48321-y
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发表时间：
2019-08-16
影响因子：
4.6
通讯作者：
Yashiro, Kenta
中科院分区：
文献类型：
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作者：
Saba, Rie;Kitajima, Keiko;Yashiro, Kenta
内皮细胞是脊椎动物心脏的内皮成分，在心脏发育中起着关键作用。然而，在胚胎发生过程中，内分泌物在何处、何时以及如何分离仍然是未知的。我们现在发现，在小鼠胚胎中，表达Sry型HMG盒基因Sox 17的Nkx 2 -5（+）心脏祖细胞（CPC）从胚胎日（E）7.5到E8.5特异性分化为内皮细胞。尽管Sox 17对于内皮细胞的命运不是必需的或足够的，但它可以使CPC的命运偏向内皮细胞。另一方面，Sox 17在内皮细胞中的表达是心脏发育所必需的。Sox 17的缺失，特别是在中胚层显着损害endoeptide发展方面的细胞增殖和行为。心肌细胞的增殖，心室小梁形成，心肌增厚也受损的非细胞自主的方式在Sox 17突变体，可能是由于下调NOTCH信号。一个未知的信号，由Sox 17调节，并需要培育心肌，是负责减少突变胚胎中的NOTCH相关基因。因此，我们的研究结果提供了深入了解分化的内皮细胞及其在心脏发育中的作用。
The endocardium is the endothelial component of the vertebrate heart and plays a key role in heart development. Where, when, and how the endocardium segregates during embryogenesis have remained largely unknown, however. We now show that Nkx2-5(+) cardiac progenitor cells (CPCs) that express the Sry-type HMG box gene Sox17 from embryonic day (E) 7.5 to E8.5 specifically differentiate into the endocardium in mouse embryos. Although Sox17 is not essential or sufficient for endocardium fate, it can bias the fate of CPCs toward the endocardium. On the other hand, Sox17 expression in the endocardium is required for heart development. Deletion of Sox17 specifically in the mesoderm markedly impaired endocardium development with regard to cell proliferation and behavior. The proliferation of cardiomyocytes, ventricular trabeculation, and myocardium thickening were also impaired in a non-cell-autonomous manner in the Sox17 mutant, likely as a consequence of down-regulation of NOTCH signaling. An unknown signal, regulated by Sox17 and required for nurturing of the myocardium, is responsible for the reduction in NOTCH-related genes in the mutant embryos. Our results thus provide insight into differentiation of the endocardium and its role in heart development.