title: Gene expression profile signatures indicate a role for Wnt signaling in endothelial commitment from embryonic stem cells.
abstract: We have used global gene expression analysis to establish a comprehensive list of candidate genes in the developing vasculature during embryonic (ES) cell differentiation in vitro. A large set of genes, including growth factors, cell surface molecules, transcriptional factors, and members of several signal transduction pathways that are known to be involved in vasculogenesis or angiogenesis, were found to have expression patterns as expected. Some unknown or functionally uncharacterized genes were differentially regulated in flk1+ cells compared with flk1- cells, suggesting possible roles for these genes in vascular commitment. Particularly, multiple components of the Wnt signaling pathway were differentially regulated in flk1+ cells, including Wnt proteins, their receptors, downstream transcriptional factors, and other components belonging to this pathway. Activation of the Wnt signal was able to expand vascular progenitor populations whereas suppression of Wnt activity reduced flk1+ populations. Suppression of Wnt signaling also inhibited the formation of matured vascular capillary-like structures during late stages of embryoid body differentiation. These data indicate a requisite and ongoing role for Wnt activity during vascular development, and the gene expression profiles identify candidate components of this pathway that participate in vascular cell differentiation.
authors.affiliation: Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Peter C
authors.initials: PC
authors.lastname: Charles
authors.forename: Yaxu
authors.initials: Y
authors.lastname: Wu
authors.forename: Rongqin
authors.initials: R
authors.lastname: Ren
authors.forename: Xinchun
authors.initials: X
authors.lastname: Pi
authors.forename: Martin
authors.initials: M
authors.lastname: Moser
authors.forename: Michal
authors.initials: M
authors.lastname: Barshishat-Kupper
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Rubin
authors.forename: Charles
authors.initials: C
authors.lastname: Perou
authors.forename: Victoria
authors.initials: V
authors.lastname: Bautch
authors.forename: Cam
authors.initials: C
authors.lastname: Patterson
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology*; D004730:Endothelium, Vascular / Q000166:cytology*; D020869:Gene Expression Profiling; D051379:Mice; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins; D040301:Vascular Endothelial Growth Factor Receptor-2