TGF-beta signaling in embryonic stem cell-derived endothelial cells.
The roles of the transforming growth factor (TGF)-beta superfamily in vasculogenesis have been implicated by the findings that mutations in genes encoding for various TGF-beta superfamily signaling components exhibit defects in vascular tissues in humans and mice. Embryonic stem cell (ESC)-derived vascular progenitor cells have been shown to differentiate into both endothelial and mural cells. We showed that members of the TGF-beta superfamily play important roles during differentiation of vascular progenitor cells derived from mouse ESC. TGF-beta inhibited proliferation and sheet formation of ESC-derived endothelial cells. Interestingly, SB-431542, a synthetic molecule that inhibits the kinases of receptors for TGF-beta and activin, facilitated proliferation and sheet formation of ESC-derived endothelial cells. We also found that stimulation of ESC-derived endothelial cells with TGF-beta resulted in phosphorylation of both Smad2 and Smadl/5; BMP induced phosphorylation of Smad1/5. In this chapter, we present how to study the cellular and biochemical effects of TGF-beta signals on endothelial cells derived from mouse ESCs.
Watabe
Tetsuro
T
Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Japan.
Yamashita
Jun K
JK
Mishima
Koichi
K
Miyazono
Kohei
K
D000818:Animals; D001549:Benzamides / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004149:Dioxoles / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D051379:Mice; D015398:Signal Transduction / Q000502:physiology*; D051896:Smad Proteins, Receptor-Regulated / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D004149:Dioxoles; D004791:Enzyme Inhibitors; D051896:Smad Proteins, Receptor-Regulated; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2