Hematopoietic stem cell development requires transient Wnt/beta-catenin activity

C Ruiz-Herguido, J Guiu, T D'Altri, J Ingles-Esteve, Elaine Dzierzak, L Espinosa, A Bigas

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Abstract

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 beta-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/beta-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 beta-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/beta-catenin activity is needed for the emergence but not the maintenance of HSCs in mouse embryos.
Original languageUndefined/Unknown
Pages (from-to)1457-1468
Number of pages12
JournalJournal of Experimental Medicine
Volume209
Issue number8
DOIs
Publication statusPublished - 2012

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