title: Temporal changes in Hox gene expression accompany endothelial cell differentiation of embryonic stem cells.
abstract: In pluripotent embryonic stem cells (ESCs), expression of the Hox master regulatory transcription factors that play essential roles in organogenesis, angiogenesis, and maintenance of differentiated tissues, is globally suppressed. We investigated whether differentiation of endothelial cells (ECs) from mouse ESCs was accompanied by activation of distinct Hox gene expression profiles. Differentiation was observed within 3 days, as indicated by the appearance of cells expressing specific endothelial marker genes (Flk-1+ /VE-Cadherin+ ). Expression of HoxA3 and HoxD3, which drive adult endothelial cell invasion and angiogenesis, peaked at day 3 and declined thereafter, whereas expression of HoxA5 and HoxD10, which maintain a mature quiescent EC phenotype, was low at day 3, but increased over time. The temporal and reciprocal changes in HoxD3 and HoxA5 expression were accompanied by corresponding changes in expression of established downstream target genes including integrin β3 and Thrombospondin-2. Our results indicate that differentiation and maturation of ECs derived from cultured ESCs mimic changes in Hox gene expression that accompany maturation of immature angiogenic endothelium into differentiated quiescent endothelium in vivo.
authors.affiliation: Department of Surgery; University of California-San Francisco, CA, USA.
authors.forename: S Bahram
authors.initials: SB
authors.lastname: Bahrami
authors.forename: Mandana
authors.initials: M
authors.lastname: Veiseh
authors.forename: Ashley A
authors.initials: AA
authors.lastname: Dunn
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Boudreau
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D005801:Genes, Homeobox / Q000502:physiology*; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D019699:Thrombospondins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D000099152:Cadherin 5; D000099262:Thrombospondin 2
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D015820:Cadherins; D039661:Integrin beta3; D034741:RNA, Small Interfering; D019699:Thrombospondins; D040301:Vascular Endothelial Growth Factor Receptor-2; D000099152:Cadherin 5; D000099262:Thrombospondin 2