Role of Hematopoietic Stem Cells in Angiogenesis

Abstract

Angiogenesis is an important event for embryonic organogenesis as well as for tissue repair in the adult. Here we show that hematopoietic stem cells (HSCs) are essential for angiogenesis during embryogenesis. To investigate the role of HSCs in endothelial cell (EC) development, we analyzed AML1-deficient embryos, which lack definitive hematopoiesis.These embryos showed defective angiogenesis in the head, pericardium, and fetal liver. Para-aortic splanchnopleural (P-Sp) explant cultures on stromal cells (P-Sp cultures) did not generate definitive hematopoietic cells and showed defective angiogenesis in theAML1-null embryo. Disrupted angiogenesis in P-Sp cultures fromAML1-null embryos was rescued by addition of HSCs. HSCs specifically produce angiopoietin-1 (Ang1).Thus HSCs, which express Ang1, directly promoted migration of ECs.These findings suggest that HSCs alone prepare the hematopoietic microenvironment.