Chen Inn-Inn, Caprioli Arianna, Ohnuki Hidetaka, Kwak Hyeongil, Porcher Catherine, Tosato Giovanna
Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford University, OX3 9DS Oxford, UK.
Sci Rep. 2016 Jun 2;6:27195. doi: 10.1038/srep27195.
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.
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人造血谱系的建立至关重要，但其出现的调控机制仍未完全明确。我们发现，内皮细胞功能的主要调节因子EphrinB2控制着产生成人型造血的内皮细胞的发育。EphrinB2的缺失会损害源自DA的造血功能。跨膜EphrinB2及其EphB4受体在新生的DA中相互作用，DA中短暂存在EphrinB2(+)和EphB4(+)内皮细胞，从而为双向细胞间信号传导提供了机会，以控制造血内皮细胞的出现。胚胎干细胞（ES）来源的EphrinB2(+)细胞富含造血内皮前体。EphrinB2沉默会损害ES细胞生成造血细胞的能力，但不会损害内皮细胞的生成。EphrinB2作为成人造血的关键调节因子的鉴定，为早期造血定向分化的调控提供了重要见解。
