The TGFβ pathway is a key player for the endothelial-to-hematopoietic transition in the embryonic aorta

The embryonic aorta produces hematopoietic stem and progenitor cells from a hemogenic endothelium localized in the aortic floor through an endothelial to hematopoietic transition. It has been long proposed that the Bone Morphogenetic Protein (BMP)/Transforming Growth Factor beta (TGF beta) signaling pathway was implicated in aortic hematopoiesis but the very nature of the signal was unknown. Here, using thorough expression analysis of the BMP/TGF beta signaling pathway members in the endothelial and hematopoietic compartments of the aorta at pre-hematopoietic and hematopoietic stages, we show that the TGF beta pathway is preferentially balanced with a prominent role of Alk1/Tgf beta R2/Smadl and 5 on both chicken and mouse species. Functional analysis using embryonic stem cells mutated for Acurl1 revealed an enhanced propensity to produce hematopoietic cells. Collectively, we reveal that TGF beta through the Alk1/Tgf beta R2 receptor axis is acting on endothelial cells to produce hematopoiesis.