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Blood, 1 April 2002, Vol. 99, No. 7, pp. 2360-2368
HEMATOPOIESIS
Macrophage colony stimulating factor modulates the
development of hematopoiesis by stimulating the differentiation of
endothelial cells in the AGM region
Ken-ichi Minehata,
Yoh-suke Mukouyama,
Takashi Sekiguchi,
Takahiko Hara, and
Atsushi Miyajima
From the Institute of Molecular and Cellular
Biosciences, The University of Tokyo, and the Core Research for
Evolutional Science and Technology of Japan Science and Technology,
Japan.
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-selectinin 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.
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