Notch1 acts via Foxc2 to promote definitive hematopoiesis via effects on hemogenic endothelium
Notch1 acts via Foxc2 to promote definitive hematopoiesis via effects on hemogenic endothelium
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DOI：
10.1182/blood-2014-04-568170
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发表时间：
2015-02-26
期刊：
影响因子：
20.3
通讯作者：
Daley, George Q.
中科院分区：
文献类型：
--
作者：
Jang, Il Ho;Lu, Yi-Fen;Daley, George Q.
造血和血管发育有许多共同的特征，包括细胞表面标记和起源部位。最近的谱系追踪研究已经确定，确定的造血干细胞和祖细胞来自血管内皮-钙粘蛋白（+）造血内皮细胞的卵巢-性腺-中肾区域，但遗传程序的规范造血内皮细胞仍然不清楚。在这里，我们发现Notch诱导增强造血潜能并促进小鼠胚胎干细胞分化培养物中造血内皮的特化，并且我们将Foxc 2鉴定为造血内皮群体中高度上调的转录物。在斑马鱼和小鼠胚胎中的研究表明，Foxc 2及其直系同源物是造血内皮细胞中确定性造血和Notch信号下游功能的适当发育所必需的。这些数据建立了在造血内皮细胞中将Notch信号传导与Foxc 2连接以促进永久性造血的途径。
Hematopoietic and vascular development share many common features, including cell surface markers and sites of origin. Recent lineage-tracing studies have established that definitive hematopoietic stem and progenitor cells arise from vascular endothelial-cadherin(+) hemogenic endothelial cells of the aorta-gonad-mesonephros region, but the genetic programs underlying the specification of hemogenic endothelial cells remain poorly defined. Here, we discovered that Notch induction enhances hematopoietic potential and promotes the specification of hemogenic endothelium in differentiating cultures of mouse embryonic stem cells, and we identified Foxc2 as a highly upregulated transcript in the hemogenic endothelial population. Studies in zebrafish and mouse embryos revealed that Foxc2 and its orthologs are required for the proper development of definitive hematopoiesis and function downstream of Notch signaling in the hemogenic endothelium. These data establish a pathway linking Notch signaling to Foxc2 in hemogenic endothelial cells to promote definitive hematopoiesis.