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First published online March 1, 2007
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2006-0556v1
25/6/1423    most recent
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Submitted on August 31, 2006
Accepted on February 20, 2007

Tissue-Specific Stem Cells

Identification of High Proliferative Potential Precursors with Hemangioblastic Activity in the Mouse AGM Region

Huiyu Yao 1, Bing Liu 1, Xiaoyan Wang 1, Yu Lan 2, Ning Hou 2, Xiao Yang 2, Ning Mao 1*

1 Department of Cell Biology, Institute of Basic Medical Sciences, Beijing, China
2 Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing, China

* To whom correspondence should be addressed. E-mail: maoning{at}nic.bmi.ac.cn.


  Abstract

Hemangioblast, a precursor possessing hematopoietic and endothelial potential, is identified as the blast colony-forming cell (BL-CFC) in the murine gastrulating embryos (E7.0-7.5). Whether hemangioblast exists in the somite-stage embryos is unknown, even though hemogenic endothelium is regarded as the precursor of definitive hematopoiesis in the aorta-gonad-mesonephros (AGM) region. To address the issue, we developed a unique three-step assay of high proliferative potential (HPP) precursors. The AGM region contained a kind of HPP precursors, which displayed hematopoietic self-renewal capacity and was able to differentiate into functional endothelial cells in vitro, i.e. incorporating Dil-Ac-LDL, expressing von Willebrand factors, and forming network structures in Matrigel. The clonal nature was verified by cell mixing assay. However, the bilineage precursor with high proliferative potential-the HPP-HA-was not readily detected in the yolk sac (E8.25-E12.5), embryonic circulation (E10.5), placenta (E10.5-E11.5), fetal liver (E11.5-E12.5) and even umbilical artery (E11.5), reflective of its strictly spatial-regulated ontogeny. Expression of CD45, a panhematopoietic marker, distinguished hematopoietic-restricted HPP-CFC from the bipotential HPP-HA. Finally, we revealed that bFGF, other than VEGF or TGF-{beta}1, was a positive modulator of the HPP-HA proliferation. Taken together, the HPP-HA represents a novel model for definitive hemangioblast in the mouse AGM region, and will shed light on molecular mechanisms underlying the hemangioblast development.

Key Words. hemangioblast, AGM, HPP-CFC, definitive hematopoiesis




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T. Era, N. Izumi, M. Hayashi, S. Tada, S. Nishikawa, and S.-I. Nishikawa
Multiple Mesoderm Subsets Give Rise to Endothelial Cells, Whereas Hematopoietic Cells Are Differentiated Only from a Restricted Subset in Embryonic Stem Cell Differentiation Culture
Stem Cells, February 1, 2008; 26(2): 401 - 411.
[Abstract] [Full Text] [PDF]


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