Macrophage colony stimulating factor modulates the development of hematopoiesis by stimulating the differentiation of endothelial cells in the AGM region.
Definitive hematopoietic stem cells arise in the aorta-gonad-mesonephros (AGM) region from hemangioblasts, common precursors for hematopoietic and endothelial cells. Previously, we showed that multipotential hematopoietic progenitors and endothelial cells were massively produced in primary culture of the AGM region in the presence of oncostatin M. Here we describe a role for macrophage-colony-stimulating factor (M-CSF) in the development of hematopoietic and endothelial cells in AGM culture. The number of hematopoietic progenitors including multipotential cells was significantly increased in the AGM culture of op/op embryos. The addition of M-CSF to op/op AGM culture decreased colony-forming unit (CFU)-GEMM, granulocyte macrophage-CFU, and erythroid-CFU, but it increased CFU-M. On the other hand, the number of cells expressing endothelial markers, vascular endothelial-cadherin, intercellular adhesion molecule 2, and Flk-1 was reduced in op/op AGM culture. The M-CSF receptor was expressed in PCLP1(+)CD45(-) cells, the precursors of endothelial cells, and M-CSF up-regulated the expression of more mature endothelial cell markers-VCAM-1, PECAM-1, and E-selectin-in PCLP1(+)CD45(-) cells. These results suggest that M-CSF modulates the development of hematopoiesis by stimulating the differentiation of PCLP-1(+)CD45(-) cells to endothelial cells in the AGM region.
Minehata
Ken-ichi
K
Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Mukouyama
Yoh-suke
YS
Sekiguchi
Takashi
T
Hara
Takahiko
T
Miyajima
Atsushi
A
D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion / Q000502:physiology*; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D017931:DNA Primers; D019040:E-Selectin / Q000494:pharmacology; D004622:Embryo, Mammalian; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects*; D015850:Interleukin-6 / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D051379:Mice; D020319:Oligodeoxyribonucleotides, Antisense; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D019010:Vascular Cell Adhesion Molecule-1 / Q000494:pharmacology; D042561:Vascular Endothelial Growth Factor B; D042582:Vascular Endothelial Growth Factor C
D016207:Cytokines; D017931:DNA Primers; D019040:E-Selectin; D016228:Endothelial Growth Factors; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D020319:Oligodeoxyribonucleotides, Antisense; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019010:Vascular Cell Adhesion Molecule-1; D042561:Vascular Endothelial Growth Factor B; D042582:Vascular Endothelial Growth Factor C; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor