成纤维细胞生长因子（FGF）信号通过调节体节Notch信号来确定造血干细胞。
FGF signalling specifies haematopoietic stem cells through its regulation of somitic Notch signalling.
作者信息
Lee Yoonsung, Manegold Jennifer E, Kim Albert D, Pouget Claire, Stachura David L, Clements Wilson K, Traver David
机构信息
Department of Cellular and Molecular Medicine and Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, California 92093, USA.
1] Department of Cellular and Molecular Medicine and Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, California 92093, USA [2] Department of Biological Sciences, California State University, Chico, California 95929, USA.
出版信息
Nat Commun. 2014 Nov 27;5:5583. doi: 10.1038/ncomms6583.
Haematopoietic stem cells (HSCs) derive from haemogenic endothelial cells of the primitive dorsal aorta (DA) during vertebrate embryogenesis. The molecular mechanisms governing this unique endothelial to haematopoietic transition remain unclear. Here, we demonstrate a novel requirement for fibroblast growth factor (FGF) signalling in HSC emergence. This requirement is non-cell-autonomous, and acts within the somite to bridge the Wnt and Notch signalling pathways. We previously demonstrated that Wnt16 regulates the somitic expression of two Notch ligands, deltaC (dlc) and deltaD (dld), whose combined function is required for HSC fate. How Wnt16 connects to Notch function has remained an open question. Our current studies demonstrate that FGF signalling, via FGF receptor 4 (Fgfr4), mediates a signal-transduction pathway between Wnt16 and Dlc, but not Dld, to regulate HSC specification. Our findings demonstrate that FGF signalling acts as a key molecular relay within the developmental HSC niche to instruct HSC fate.
造血干细胞（HSCs）在脊椎动物胚胎发育过程中起源于原始背主动脉（DA）的造血内皮细胞。控制这种独特的内皮细胞向造血细胞转变的分子机制仍不清楚。在此，我们证明了成纤维细胞生长因子（FGF）信号在造血干细胞出现过程中的新需求。这种需求是非细胞自主的，并且在体节内起作用以连接Wnt和Notch信号通路。我们之前证明Wnt16调节两种Notch配体deltaC（dlc）和deltaD（dld）的体节表达，其联合功能是造血干细胞命运所必需的。Wnt16如何与Notch功能联系仍然是一个悬而未决的问题。我们目前的研究表明，FGF信号通过FGF受体4（Fgfr4）介导Wnt16和Dlc之间而非Dld之间的信号转导途径，以调节造血干细胞的特化。我们的研究结果表明，FGF信号在发育中的造血干细胞生态位内作为关键的分子中继来指导造血干细胞的命运。
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