成纤维细胞生长因子（FGF）信号通过调节骨形态发生蛋白（BMP）信号通路来限制造血干细胞的特化。
FGF signalling restricts haematopoietic stem cell specification via modulation of the BMP pathway.
作者信息
Pouget Claire, Peterkin Tessa, Simões Filipa Costa, Lee Yoonsung, Traver David, Patient Roger
机构信息
1] Department of Cellular and Molecular Medicine, Section of Cell and Developmental Biology, University of California, La Jolla, San Diego, California 92093, USA [2] MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX1 9DS, UK.
MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX1 9DS, UK.
出版信息
Nat Commun. 2014 Nov 27;5:5588. doi: 10.1038/ncomms6588.
Haematopoietic stem cells (HSCs) are produced during embryogenesis from the floor of the dorsal aorta. The localization of HSCs is dependent on the presence of instructive signals on the ventral side of the vessel. The nature of the extrinsic molecular signals that control the aortic haematopoietic niche is currently poorly understood. Here we demonstrate a novel requirement for FGF signalling in the specification of aortic haemogenic endothelium. Our results demonstrate that FGF signalling normally acts to repress BMP activity in the subaortic mesenchyme through transcriptional inhibition of bmp4, as well as through activation of two BMP antagonists, noggin2 and gremlin1a. Taken together, these findings demonstrate a key role for FGF signalling in establishment of the developmental HSC niche via its regulation of BMP activity in the subaortic mesenchyme. These results should help inform strategies to recapitulate the development of HSCs in vitro from pluripotent precursors.
造血干细胞（HSCs）在胚胎发育过程中由背主动脉底部产生。造血干细胞的定位取决于血管腹侧存在的诱导信号。目前对控制主动脉造血微环境的外在分子信号的性质了解甚少。在这里，我们证明了FGF信号在主动脉造血内皮细胞特化过程中的新需求。我们的结果表明，FGF信号通常通过对bmp4的转录抑制以及通过激活两种BMP拮抗剂noggin2和gremlin1a来抑制主动脉下间充质中的BMP活性。综上所述，这些发现表明FGF信号通过调节主动脉下间充质中的BMP活性，在发育中的造血干细胞微环境的建立中起关键作用。这些结果应有助于为从多能前体体外重现造血干细胞发育的策略提供信息。
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