Hematopoietic stem cell development requires transient Wnt/β-catenin activity.
Understanding how hematopoietic stem cells (HSCs) are generated and the signals that control this process is a crucial issue for regenerative medicine applications that require in vitro production of HSC. HSCs emerge during embryonic life from an endothelial-like cell population that resides in the aorta-gonad-mesonephros (AGM) region. We show here that β-catenin is nuclear and active in few endothelial nonhematopoietic cells closely associated with the emerging hematopoietic clusters of the embryonic aorta during mouse development. Importantly, Wnt/β-catenin activity is transiently required in the AGM to generate long-term HSCs and to produce hematopoietic cells in vitro from AGM endothelial precursors. Genetic deletion of β-catenin from the embryonic endothelium stage (using VE-cadherin-Cre recombinase), but not from embryonic hematopoietic cells (using Vav1-Cre), precludes progression of mutant cells toward the hematopoietic lineage; however, these mutant cells still contribute to the adult endothelium. Together, those findings indicate that Wnt/β-catenin activity is needed for the emergence but not the maintenance of HSCs in mouse embryos.
Program in Cancer Research, Institut Hospital del Mar d'Investigacions Mèdiques, Parc de Recerca Biomèdica de Barcelona, 08003 Barcelona, Spain.
Cristina
C
Ruiz-Herguido
Jordi
J
Guiu
Teresa
T
D'Altri
Julia
J
Inglés-Esteve
Elaine
E
Dzierzak
Lluis
L
Espinosa
Anna
A
Bigas
D000818:Animals; D001011:Aorta / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism; D006066:Gonads / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008650:Mesonephros / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
C495267:CTNNB1 protein, mouse; D051153:Wnt Proteins; D051176:beta Catenin