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Blood, 15 June 2005, Vol. 105, No. 12, pp. 4590-4597.
Prepublished online as a Blood First Edition Paper on February 22, 2005; DOI 10.1182/blood-2004-10-4137.
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Submitted October 28, 2004
Accepted February 8, 2005
The homeobox gene HEX regulates proliferation and differentiation of hemangioblasts and endothelial cells during ES cell differentiation
Atsushi Kubo, Vincent Chen, Marion Kennedy, Elizabeth Zahradka, George Q Daley, and Gordon Keller*
The Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY, USA
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts, USA
* Corresponding author; email: gordon.keller{at}mssm.edu.
In this report we have investigated the role of the homeobox gene Hex in the development and differentiation of the blast colony-forming cell (BL-CFC), a progenitor with hemangioblast characteristics generated in ES cell-derived embryoid bodies (EBs). Molecular analysis showed that Hex is expressed in mesoderm, in populations that contain BL-CFC and in blast cell colonies, the progeny of the BL-CFC. Hex-/- EBs displayed a defect in macrophage development, but generated higher numbers of BL-CFC than wild type EBs. In addition to differences in these progenitor populations, we also found that endothelial cells from the Hex-/- EBs showed enhanced proliferative potential compared to those from wild type EBs. Forced expression of Hex at the onset of ES cell differentiation resulted in reduced EB cellularity, Flk-1 expression and BL-CFC development. Taken together, these findings demonstrate that Hex functions at multiple stages of development within the differentiating EBs and uncover a novel role for this transcription factor as a negative regulator of the hemangioblast and the endothelial lineage.
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