EphrinB2 regulates the emergence of a hemogenic endothelium from the aorta.
EphrinB2 regulates the emergence of a hemogenic endothelium from the aorta.
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DOI：
10.1038/srep27195
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发表时间：
2016-06-02
影响因子：
4.6
通讯作者：
Tosato G
中科院分区：
文献类型：
--
作者：
Chen II;Caprioli A;Ohnuki H;Kwak H;Porcher C;Tosato G
成人型胚胎内造血起源于背主动脉（DA）的特化内皮细胞。尽管这种特化内皮对于造血干细胞和成体造血谱系的建立至关重要，但调节其出现的机制尚不完全清楚。我们发现EphrinB2是内皮细胞功能的主要调节因子，它控制着内皮细胞生成成人型造血的发展。EphrinB2的缺乏损害DA衍生的造血。跨膜EphrinB2及其EphB4受体在新生的DA中相互作用，其瞬时地窝藏EphrinB2+和EphB4+内皮细胞，从而提供双向细胞间信号传导的机会以控制生血内皮的出现。胚胎干（ES）细胞衍生的EphrinB2+细胞富含生血内皮前体。EphrinB2沉默损害造血细胞的ES生成，但不损害内皮细胞的生成。EphrinB2作为成人造血的重要调节因子的鉴定为早期造血定型的调节提供了重要的见解。
Adult-type intraembryonic hematopoiesis arises from specialized endothelial cells of the dorsal aorta (DA). Despite the critical importance of this specialized endothelium for establishment of hematopoietic stem cells and adult hematopoietic lineages, the mechanisms regulating its emergence are incompletely understood. We show that EphrinB2, a principal regulator of endothelial cell function, controls the development of endothelium producing adult-type hematopoiesis. The absence of EphrinB2 impairs DA-derived hematopoiesis. Transmembrane EphrinB2 and its EphB4 receptor interact in the emerging DA, which transiently harbors EphrinB2+ and EphB4+ endothelial cells, thereby providing an opportunity for bi-directional cell-to-cell signaling to control the emergence of the hemogenic endothelium. Embryonic Stem (ES) cell-derived EphrinB2+ cells are enriched with hemogenic endothelial precursors. EphrinB2 silencing impairs ES generation of hematopoietic cells but not generation of endothelial cells. The identification of EphrinB2 as an essential regulator of adult hematopoiesis provides important insight in the regulation of early hematopoietic commitment.