The homeobox gene HEX regulates proliferation and differentiation of hemangioblasts and endothelial cells during ES cell differentiation.
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 embryonic stem (ES) cell-derived embryoid bodies (EBs). Molecular analysis showed that Hex is expressed in mesoderm, in populations that contain BL-CFCs, and in blast cell colonies, the progeny of the BL-CFCs. Hex(-/-) EBs displayed a defect in macrophage development but generated higher numbers of BL-CFCs than did 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 with those from wild-type EBs. Forced expression of Hex at the onset of ES cell differentiation resulted in reduced EB cellularity, fetal liver kinase-1 (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.
Kubo
Atsushi
A
Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Chen
Vincent
V
Kennedy
Marion
M
Zahradka
Elizabeth
E
Daley
George Q
GQ
Keller
Gordon
G
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002469:Cell Separation; D018076:DNA, Complementary / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology*; D004730:Endothelium, Vascular / Q000166:cytology*; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D018919:Neovascularization, Physiologic; D009474:Neurons / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D018076:DNA, Complementary; C513080:Hhex protein, mouse; D018398:Homeodomain Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014157:Transcription Factors
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