Open AccessWnt5a Regulates Hematopoietic Stem Cell Proliferation and Repopulation Through the Ryk Receptor
Author(s) -
Povinelli Benjamin J.,
Nemeth Michael J.
Publication year - 2014
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1513
Subject(s) - biology , wnt5a , stem cell , haematopoiesis , microbiology and biotechnology , hematopoietic stem cell , repopulation , receptor , cell growth , cancer research , immunology , signal transduction , genetics , wnt signaling pathway
Proper regulation of the balance between hematopoietic stem cell (HSC) proliferation, self‐renewal, and differentiation is necessary to maintain hematopoiesis throughout life. The Wnt family of ligands has been implicated as critical regulators of these processes through a network of signaling pathways. Previously, we have demonstrated that the Wnt5a ligand can induce HSC quiescence through a noncanonical Wnt pathway, resulting in an increased ability to reconstitute hematopoiesis. In this study, we tested the hypothesis that the Ryk protein, a Wnt ligand receptor that can bind the Wnt5a ligand, regulated the response of HSCs to Wnt5a. We observed that inhibiting Ryk blocked the ability of Wnt5a to induce HSC quiescence and enhance short‐term and long‐term hematopoietic repopulation. We found that Wnt5a suppressed production of reactive oxygen species, a known inducer of HSC proliferation. The ability of Wnt5a to inhibit ROS production was also regulated by Ryk. From these data, we propose that Wnt5a regulates HSC quiescence and hematopoietic repopulation through the Ryk receptor and that this process is mediated by suppression of reactive oxygen species. S tem C ells 2014;32:105–115