Role of hematopoietic stem cells in angiogenesis.
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 the AML1-null embryo. Disrupted angiogenesis in P-Sp cultures from AML1-null embryos was rescued by addition of HSCs. HSCsspecifically produce angiopoietin-1 (Ang1). Thus HSCs,which expressAng1, directly promoted migration of ECs. These findings suggest that HSCs alone prepare the hematopoietic microenvironment.
Suda
T
T
Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University, Japan. sudato@gpo.kumamoto-u.ac.jp
Takakura
N
N
D042683:Angiopoietin-1; D000818:Animals; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D004622:Embryo, Mammalian / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000196:embryology; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology
D042683:Angiopoietin-1; C467628:Angpt1 protein, mouse; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; C493726:Runx1 protein, mouse; D014157:Transcription Factors