Wnt5a inhibits canonical Wnt signaling in hematopoietic stem cells and enhances repopulation
Wnt5a inhibits canonical Wnt signaling in hematopoietic stem cells and enhances repopulation
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DOI：
10.1073/pnas.0704747104
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发表时间：
2007-09-25
影响因子：
11.1
通讯作者：
Bodine, David M.
中科院分区：
文献类型：
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作者：
Nemeth, Michael J.;Topol, Lilia;Bodine, David M.
调节造血干细胞（HSC）增殖和多系分化之间命运决定的机制尚不清楚。Wnt家族的配体成员激活典型的Writ信号通路，它利用β -连环蛋白来传递信号，已被证明可以调节HSC的功能。在这项研究中，我们研究了非规范的Writ信号在调节HSC命运中的作用。我们观察到，非典型性Wnt5a抑制了HSC中wnt3a介导的典型性Writ信号，并抑制了wnt3a介导的与HSC分化相关的基因表达改变，如myc的表达增加。Wnt5a通过维持HSC处于静止Go状态来增加短期和长期HSC的再生。根据这些数据，我们提出Wnt5a通过拮抗典型的Writ通路来调节造血，从而产生一群静止的hsc。
The mechanisms that regulate hematopoietic stem cell (HSC) fate decisions between proliferation and multilineage differentiation are unclear. Members of the Wnt family of ligands that activate the canonical Writ signaling pathway, which utilizes beta-catenin to relay the signal, have been demonstrated to regulate HSC function. In this study, we examined the role of noncanonical Writ signaling in regulating HSC fate. We observed that noncanonical Wnt5a inhibited Wnt3a-mediated canonical Writ signaling in HSCs and suppressed Wnt3a-mediated alterations in gene expression associated with HSC differentiation, such as increased expression of myc. Wnt5a increased short- and long-term HSC repopulation by maintaining HSCs in a quiescent Go state. From these data, we propose that Wnt5a regulates hematopoiesis by the antagonism of the canonical Writ pathway, resulting in a pool of quiescent HSCs.