Wnt9a Is Required for the Aortic Amplification of Nascent Hematopoietic Stem Cells.

Wnt9a Is Required for the Aortic Amplification of Nascent Hematopoietic Stem Cells.
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DOI:
10.1016/j.celrep.2016.10.027
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发表时间:
2016-11-01
期刊:
影响因子:
8.8
通讯作者:
Willert K
Willert K
中科院分区:
生物学1区
文献类型:
--
作者:
Grainger S;Richter J;Palazón RE;Pouget C;Lonquich B;Wirth S;Grassme KS;Herzog W;Swift MR;Weinstein BM;Traver D;Willert K

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成年动物中的所有成熟血细胞类型都来自造血干细胞和祖细胞(HSPC)。然而,调控HSPC个体发育的发育线索还不完全清楚。特别是,围绕成熟HSPC发育中Wnt/β-连环蛋白信号传导需求的细节是有争议的,难以巩固。我们使用斑马鱼证明,Wnt信号传导是指导主动脉中HSPC扩增所需的。Wnt 9a是这一过程中特别需要的,不能被Wnt 9 b或Wnt 3a取代。这种增殖事件的发生与初始HSPC命运规格无关,并且在主动脉形成之前需要Wnt 9a输入。HSPC动脉扩增发生在接种次级造血组织之前,并部分通过细胞周期调节因子myca(c-myc)进行。我们的研究结果支持一个一般的范式,其中早期信号事件,包括Wnt,指导后来的HSPC发育过程。造血干细胞和祖细胞(HSPC)产生成人生物体的所有血细胞;然而,这些细胞在体内是如何衍生的仍然不完全清楚。Grainger等人使用斑马鱼发现,Wnt 9a在HSPC迁移到次级造血位点之前介导HSPC的扩增。
All mature blood cell types in the adult animal arise from hematopoietic stem and progenitor cells (HSPCs). However, the developmental cues regulating HSPC ontogeny are incompletely understood. In particular, the details surrounding a requirement for Wnt/β-catenin signaling in the development of mature HSPCs are controversial and difficult to consolidate. Using zebrafish, we demonstrate that Wnt signaling is required to direct an amplification of HSPCs in the aorta. Wnt9a is specifically required for this process and cannot be replaced by Wnt9b or Wnt3a. This proliferative event occurs independently of initial HSPC fate specification, and the Wnt9a input is required prior to aorta formation. HSPC arterial amplification occurs prior to seeding of secondary hematopoietic tissues and proceeds, in part, through the cell cycle regulator myca (c-myc). Our results support a general paradigm, in which early signaling events, including Wnt, direct later HSPC developmental processes. Hematopoietic stem and progenitor cells (HSPCs) give rise to all of the blood cells of the adult organism; however, how these cells are derived in vivo is still incompletely understood. Using zebrafish, Grainger et al. find that Wnt9a mediates amplification of HSPCs prior to their migration to secondary hematopoietic sites.
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