Abstract：
Generation of hematopoietic stem and progenitor cells (HSPCs) ex vivo and in vivo, especially the generation of safe therapeutic HSPCs, still remains inefficient. In this study, we have identified compound BF170 hydrochloride as a previously unreported pro-hematopoiesis molecule, using the differentiation assays of primary zebrafish blastomere cell culture and mouse embryoid bodies (EBs), and we demonstrate that BF170 hydrochloride promoted definitive hematopoiesis in vivo. During zebrafish definitive hematopoiesis, BF170 hydrochloride increases blood flow, expands hemogenic endothelium (HE) cells and promotes HSPC emergence. Mechanistically, the primary cilia-Ca2+-Notch/NO signaling pathway, which is downstream of the blood flow, mediated the effects of BF170 hydrochloride on HSPC induction in vivo. Our findings, for the first time, reveal that BF170 hydrochloride is a compound that enhances HSPC induction and may be applied to the ex vivo expansion of HSPCs.
摘要：
体外和体内造血干细胞和祖细胞（HSPCs）的产生，特别是安全治疗性HSPCs的产生，仍然效率低下。在这项研究中,我们已经确定化合物BF170盐酸盐是以前未报道的促造血分子，使用原代斑马鱼卵裂球细胞培养物和小鼠胚状体（EB）的分化测定，我们证明了BF170盐酸盐在体内促进了确定的造血作用。在斑马鱼确定的造血过程中，BF170盐酸盐增加血流量，扩大血源性内皮（HE）细胞，促进HSPC的出现。机械上,初级纤毛-Ca2+-Notch/NO信号通路,它是血流的下游，在体内介导盐酸BF170对HSPC的诱导作用。我们的发现,第一次,揭示了BF170盐酸盐是增强HSPC诱导的化合物,并且可以应用于HSPC的离体扩增。
