A role for hematopoietic stem cells in promoting 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) play important roles 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 and pericardium. Para-aortic splanchnopleural (P-Sp) explant cultures on stromal cells (P-Sp culture) 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 or angiopoietin-1 (Ang1). HSCs, which express Ang1, directly promoted migration of ECs in vivo and in vitro. These results indicate that HSCs are critical for angiogenesis.
Takakura
N
N
Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Japan. ntakaku@gpo.kumamoto-u.ac.jp
Watanabe
T
T
Suenobu
S
S
Yamada
Y
Y
Noda
T
T
Ito
Y
Y
Satake
M
M
Suda
T
T
D042683:Angiopoietin-1; D000818:Animals; D002460:Cell Line; D050676:Core Binding Factor Alpha 2 Subunit; D046508:Culture Techniques; D004268:DNA-Binding Proteins / Q000235:genetics; D015870:Gene Expression; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009363:Neoplasm Proteins / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology*; D020286:Pericytes / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D014157:Transcription Factors / Q000235:genetics
D042683:Angiopoietin-1; C467628:Angpt1 protein, mouse; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; C105373:MEN1 protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; C493726:Runx1 protein, mouse; D014157:Transcription Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor