New insights to vascular smooth muscle cell and pericyte differentiation of mouse embryonic stem cells in vitro

Arteriosclerosis, Thrombosis, and Vascular Biology
Henrik LindskogP Lindahl

Abstract

The molecular mechanisms that regulate pericyte differentiation are not well understood, partly because of the lack of well-characterized in vitro systems that model this process. In this article, we develop a mouse embryonic stem (ES) cell-based angiogenesis/vasculogenesis assay and characterize the system for vascular smooth muscle cell (VSMC) and pericyte differentiation. ES cells that were cultured for 5 days on OP9 stroma cells upregulated their transcription of VSMC and pericyte selective genes. Other SMC marker genes were induced at a later time point, which suggests that vascular SMC/pericyte genes are regulated by a separate mechanism. Moreover, sequence analysis failed to identify any conserved CArG elements in the vascular SMC and pericyte gene promoters, which indicates that serum response factor is not involved in their regulation. Gleevec, a tyrosine kinase inhibitor that blocks platelet-derived growth factor (PDGF) spell-receptor signaling, and a neutralizing antibody against transforming growth factor (TGF) beta1, beta2, and beta3 failed to inhibit the induction of vascular SMC/pericyte genes. Finally, ES-derived vascular sprouts recruited cocultured MEF cells to pericyte-typical locations. The recruited cells a...Continue Reading

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Citations

Nov 10, 2010·Cellular and Molecular Neurobiology·Masahiro KamouchiTakanari Kitazono
Jan 15, 2014·Seminars in Cancer Biology·Eliane CortezKristian Pietras
Nov 9, 2017·Genome Biology·Florian BuettnerOliver Stegle
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