Wnt5a inhibits canonical Wnt signaling in hematopoietic stem cells and enhances repopulation

被引：234

作者：

Nemeth, Michael J.

Topol, Lilia

Anderson, Stacie M.

Yang, Yingzi

Bodine, David M.

机构：

[1] NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA

[2] NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2007年 / 104卷 / 39期

关键词：

cell cycle; hematopoiesis; hematopoietic stem cell transplantation;

D O I：

10.1073/pnas.0704747104

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 [理学]; 0710 [生物学]; 09 [农学];

摘要：

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.

引用

页码：15436 / 15441

页数：6

共 38 条

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