TY - JOUR
T1 - Hematopoietic stem cell development requires transient Wnt/β-catenin activity
AU - Ruiz-Herguido, Cristina
AU - Guiu, Jordi
AU - D'Altri, Teresa
AU - Inglés-Esteve, Julia
AU - Dzierzak, Elaine
AU - Espinosa, Lluis
AU - Bigas, Anna
PY - 2012/7/1
Y1 - 2012/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84866443757&partnerID=8YFLogxK
U2 - 10.1084/jem.20120225
DO - 10.1084/jem.20120225
M3 - Journal article
C2 - 22802352
AN - SCOPUS:84866443757
SN - 0022-1007
VL - 209
SP - 1457
EP - 1468
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 8
ER -