The Wave2 scaffold Hem-1 is required for transition of fetal liver hematopoiesis to bone marrow.
The Wave2 scaffold Hem-1 is required for transition of fetal liver hematopoiesis to bone marrow.
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DOI：
10.1038/s41467-018-04716-5
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发表时间：
2018-06-18
影响因子：
16.6
通讯作者：
Hromas RA
中科院分区：
文献类型：
--
作者：
Shao L;Chang J;Feng W;Wang X;Williamson EA;Li Y;Schajnovitz A;Scadden D;Mortensen LJ;Lin CP;Li L;Paulson A;Downing J;Zhou D;Hromas RA
造血从胎肝（FL）到骨髓（BM）的过渡特征不完全。我们证明了Wiskott-Aldrich综合征的尿脯氨酸同源蛋白（WAVE）复合物2是这种转变所必需的，因为通过删除其支架Hem-1的复合物降解导致新生儿BM造血干细胞（HSC）的过早耗尽。BM HSC的这种耗尽是由于Hem-1−/− FL HSC的BM植入失败，导致早期死亡。Hem-1−/− FL HSC的植入缺陷不是由于WAVE 2复合物的典型功能（肌动蛋白聚合的调节）的缺乏，因为来自Hem-1−/−小鼠的FL HSC在趋化性、BM归巢或粘附方面没有表现出缺陷。相反，Hem-1−/− FL HSC在骨髓中植入失败是由于WAVE 2复合物降解导致c-Abl存活信号丢失。然而，c-Abl活性对于成年BM HSC向BM中的植入是不利的。这些发现揭示了WAVE 2复合物的一种新功能，并定义了FL HSC在胚胎BM生态位中适应性的机制。造血干细胞（HSCs）在胚胎发生期间从胎儿肝脏迁移到骨髓（BM）。在这里，作者表明WAVE 2复合物支架Hem 1是骨髓中HSC植入所需的，不是通过其调节肌动蛋白聚合的典型作用，而是通过c-Abl存活信号传导。
The transition of hematopoiesis from the fetal liver (FL) to the bone marrow (BM) is incompletely characterized. We demonstrate that the Wiskott–Aldrich syndrome verprolin-homologous protein (WAVE) complex 2 is required for this transition, as complex degradation via deletion of its scaffold Hem-1 causes the premature exhaustion of neonatal BM hematopoietic stem cells (HSCs). This exhaustion of BM HSC is due to the failure of BM engraftment of Hem-1−/− FL HSCs, causing early death. The Hem-1−/− FL HSC engraftment defect is not due to the lack of the canonical function of the WAVE2 complex, the regulation of actin polymerization, because FL HSCs from Hem-1−/− mice exhibit no defects in chemotaxis, BM homing, or adhesion. Rather, the failure of Hem-1−/− FL HSC engraftment in the marrow is due to the loss of c-Abl survival signaling from degradation of the WAVE2 complex. However, c-Abl activity is dispensable for the engraftment of adult BM HSCs into the BM. These findings reveal a novel function of the WAVE2 complex and define a mechanism for FL HSC fitness in the embryonic BM niche. Hematopoietic stem cells (HSCs) migrate from the fetal liver to the bone marrow (BM) during embryogenesis. Here the authors show that the WAVE2 complex scaffold Hem1 is required for engraftment of HSCs in BM, not through its canonical role regulating actin polymerization, but through c-Abl survival signaling.
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影响因子：
16
作者：
Lebensohn AM;Kirschner MW
通讯作者：
Kirschner MW
肌动蛋白调节波复合物的结构和控制。
影响因子：
64.8
作者：
Chen, Zhucheng;Borek, Dominika;Padrick, Shae B.;Gomez, Timothy S.;Metlagel, Zoltan;Ismail, Ayman M.;Umetani, Junko;Billadeau, Daniel D.;Otwinowski, Zbyszek;Rosen, Michael K.
通讯作者：
Rosen, Michael K.
影响因子：
12.3
作者：
Kurisu S;Takenawa T
通讯作者：
Takenawa T
影响因子：
7.2
作者：
Devreotes, Peter;Horwitz, Alan Rick
通讯作者：
Horwitz, Alan Rick
影响因子：
20.3
作者：
Pye, Seonaid M.;Cortes, Jorge;Apperley, Jane F.
通讯作者：
Apperley, Jane F.