Hematopoietic stem cell development requires transient Wnt/β-catenin activity
The Journal of Experimental Medicine , Volume 209 - Issue 8 p. 1457- 1468
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.
|The Journal of Experimental Medicine|
|Organisation||Biophysical Genomics, Department Cell Biology & Genetics|
Ruiz-Herguido, C, Guiu, J, D'Altri, C, Inglés-Esteve, J, Dzierzak, E.A, Espinosa, L, & Bigas, A. (2012). Hematopoietic stem cell development requires transient Wnt/β-catenin activity. The Journal of Experimental Medicine, 209(8), 1457–1468. doi:10.1084/jem.20120225