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

Abstract:

: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 Wnt 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 Wnt signaling in regulating HSC fate. We observed that noncanonical Wnt5a inhibited Wnt3a-mediated canonical Wnt 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 G(0) state. From these data, we propose that Wnt5a regulates hematopoiesis by the antagonism of the canonical Wnt pathway, resulting in a pool of quiescent HSCs.

authors

Nemeth MJ,Topol L,Anderson SM,Yang Y,Bodine DM

doi

10.1073/pnas.0704747104

subject

Has Abstract

pub_date

2007-09-25 00:00:00

pages

15436-41

issue

39

eissn

0027-8424

issn

1091-6490

pii

0704747104

journal_volume

104

pub_type

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