Wnt5a inhibits canonical Wnt signaling in hematopoietic stem cells and enhances repopulation.
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.
Nemeth
Michael J
MJ
Genetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, MD 20892-4442, USA.
Topol
Lilia
L
Anderson
Stacie M
SM
Yang
Yingzi
Y
Bodine
David M
DM
D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D008957:Models, Genetic; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*; D000071818:Wnt-5a Protein; D060508:Wnt3 Protein; D060509:Wnt3A Protein
D008024:Ligands; C555510:WNT3A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; C438615:Wnt5a protein, mouse