Molecular mechanism of self-renewal exit during endothelial differentiation

QUE JIANWEN

Publication

Molecular mechanism of self-renewal exit during endothelial differentiation

QUE JIANWEN

Abstract

Endothelial differentiation during vasculogenesis proceeds through many sequential transitional embryonic cell stages. To understand the mechanism of this process, a cellular model of endothelial differentiation was established by isolating some endothelial progenitor cells as cell lines (RoSH 1, 2 to 13) from mouse embryos. These lines are euploid and do not express pluripotency markers. They can be induced to differentiate into functional endothelial cells in vitro and in vivo. RoSH2 cells were used to study the mechanism of endothelial differentiation and in the investigation of the inhibition of self-renewal. PI3K/mTOR-mediated translational regulation was identified to be a key mechanism in this process. Inhibiting the mTOR pathway resulted in spontaneous differentiation. Cyclins D2 and E1, which regulates the G1/S progression during self-renewal, were identified to be two targets of this pathway. Understanding the major signaling pathway and its main targets during the initiation of differentiation will provide new insights into vasculogenesis.