title: The homeobox gene HEX regulates proliferation and differentiation of hemangioblasts and endothelial cells during ES cell differentiation.
abstract: 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.
authors.affiliation: Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kubo
authors.forename: Vincent
authors.initials: V
authors.lastname: Chen
authors.forename: Marion
authors.initials: M
authors.lastname: Kennedy
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Zahradka
authors.forename: George Q
authors.initials: GQ
authors.lastname: Daley
authors.forename: Gordon
authors.initials: G
authors.lastname: Keller
mesh_terms: 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
chemical_list: D018076:DNA, Complementary; C513080:Hhex protein, mouse; D018398:Homeodomain Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014157:Transcription Factors
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