Institut Pasteur, Department of Developmental &Stem Cell Biology, Paris 75015, France.
CNRS, URA2578, Paris 75015, France.
Nat Commun. 2015 Sep 28;6:8375. doi: 10.1038/ncomms9375.
The ontogeny of haematopoietic niches in vertebrates is essentially unknown. Here we show that the stromal cells of the caudal haematopoietic tissue (CHT), the first niche where definitive haematopoietic stem/progenitor cells (HSPCs) home in zebrafish development, derive from the caudal somites through an epithelial-mesenchymal transition (EMT). The resulting stromal cell progenitors accompany the formation of the caudal vein sinusoids, the other main component of the CHT niche, and mature into reticular cells lining and interconnecting sinusoids. We characterize a zebrafish mutant defective in definitive haematopoiesis due to a deficiency in the nascent polypeptide-associated complex alpha subunit (NACA). We demonstrate that the defect resides not in HSPCs but in the CHT niche. NACA-deficient stromal cell progenitors initially develop normally together with the sinusoids, and HSPCs home to the resulting niche, but stromal cell maturation is compromised, leading to a niche that is unable to support HSPC maintenance, expansion and differentiation.
脊椎动物造血龛的个体发生基本上是未知的。在这里，我们表明，在斑马鱼发育过程中，第一个确定的造血干/祖细胞 (HSPC) 归巢的尾造血组织 (CHT) 的基质细胞来自尾部体节，通过上皮-间充质转化 (EMT) 产生。由此产生的基质细胞祖细胞伴随着尾静脉窦的形成，这是 CHT 龛的另一个主要组成部分，成熟为排列和相互连接窦的网状细胞。我们描述了一种由于新生多肽相关复合物α亚基 (NACA) 缺陷而导致定型造血功能缺陷的斑马鱼突变体。我们证明缺陷不在于 HSPCs，而在于 CHT 龛。NACA 缺陷的基质细胞祖细胞最初与窦一起正常发育，HSPCs归巢到由此产生的龛，但基质细胞成熟受损，导致龛无法支持 HSPC 的维持、扩增和分化。
