Gene Expression Profile Signatures Indicate a Role for Wnt Signaling in Endothelial Commtment From Embryonic Stem Cells

ABSTRACT: Embryonic stem (ES) cells have the potential to generate a variety of cell lineages including endothelial cells, blood cells and smooth muscle cells. flk1-expressing cells derived from ES cells serve as vascular progenitors. We have used global gene expression analysis in order to establish a comprehensive list of candidate genes in the developing vasculature during 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 EB 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. Keywords: Time course, development, endothelial cell, angiogenesis, embryonic stem cells, mouse, vasculature, Wnt signaling

ORGANISM(S): Mus musculus

PROVIDER: GSE3757 | GEO | 2006/05/23

SECONDARY ACCESSION(S): PRJNA93931

REPOSITORIES: GEO