Polarized expression of bone morphogenetic protein-4 in the human aorta-gonad-mesonephros region

In the mammal, definitive hematopoietic stem cells (HSCs) are first derived from mesodermal cells within a region of the embryonic para-aortic splanch nopleura known as the aorta-gonad-mesonephros (AGM), Within this region, HS Cs are thought to arise from hemangioblast precursors located in the ventra l wall of the dorsal aorta. However, the factors that regulate HSC developm ent in vivo are still largely unknown, Bone morphogenetic protein (BMP)-4, a member of the transforming growth factor beta (TGF-beta) superfamily of g rowth factors, is a potent ventralizing factor and has been implicated in t he commitment of embryonic mesodermal cells to a hematopoietic fate in a nu mber of systems. In the human AGM, we find that BMP-4 is expressed at high levels, and with striking polarity, in a region of densely packed cells und erlying intra-aortic hematopoietic clusters. In contrast, TGF-beta 1 is exp ressed predominantly by hematopoietic cells within the clusters. These find ings implicate both BMP-4 and TGF-beta 1 in the initiation and regulation o f hematopoiesis in the human AGM, Furthermore, the distribution of BMP-4 ex pression is highly suggestive of a direct role in the specification of huma n hematopoietic cells from embryonic mesoderm in vivo.(Blood. 2000;96:1591- 1593) (C) 2000 by The American Society of Hematology.