FGF signalling restricts haematopoietic stem cell specification via modulation of the BMP pathway.
FGF signalling restricts haematopoietic stem cell specification via modulation of the BMP pathway.
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DOI：
10.1038/ncomms6588
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发表时间：
2014-11-27
影响因子：
16.6
通讯作者：
Patient, Roger
中科院分区：
文献类型：
--
作者：
Pouget, Claire;Peterkin, Tessa;Simoes, Filipa Costa;Lee, Yoonsung;Traver, David;Patient, Roger
造血干细胞（HSC）是在胚胎发生过程中从背主动脉底部产生的。HSC的定位依赖于血管腹侧存在的指导性信号。目前对控制主动脉造血生态位的外在分子信号的性质知之甚少。在这里，我们证明了一个新的要求FGF信号在主动脉生血内皮细胞的规格。我们的研究结果表明，FGF信号通常通过抑制BMP 4的转录，以及通过激活两个BMP拮抗剂，noggin 2和gremlin 1a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信号传导通过调节主动脉下间充质中BMP活性在建立发育HSC生态位中的关键作用。这些结果应该有助于告知策略，以概括从多能前体体外HSC的发展。
Hematopoietic stem cells (HSCs) are produced during embryogenesis from the floor of the dorsal aorta. The localization of HSCs is dependent upon the presence of instructive signals on the ventral side of the vessel. The nature of the extrinsic molecular signals that control the aortic hematopoietic niche is currently poorly understood. Here we demonstrate a novel requirement for FGF signaling in the specification of aortic hemogenic endothelium. Our results demonstrate that FGF signaling 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 signaling 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.
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影响因子：
9.2
作者：
Iida, Atsuo;Sakaguchi, Kazuya;Sehara-Fujisawa, Atsuko
通讯作者：
Sehara-Fujisawa, Atsuko
影响因子：
4.6
作者：
Groves, JA;Hammond, CL;Hughes, SM
通讯作者：
Hughes, SM
DOI：
10.1073/pnas.0706923105
发表时间：
2007-12-26
影响因子：
11.1
作者：
Durand, Charles;Robin, Catherine;Dzierzak, Elaine
通讯作者：
Dzierzak, Elaine
影响因子：
10.5
作者：
Burns, CE;Traver, D;Zon, LI
通讯作者：
Zon, LI
影响因子：
2.7
作者：
Fouquet, B;Weinstein, BM;Fishman, MC
通讯作者：
Fishman, MC