PI3 K/Akt/mTOR-Mediated Translational Control Regulates Proliferation and Differentiation of Lineage-Restricted RoSH Stem Cell Lines
El Oakley, Reida M
MetadataShow full item record
CitationQue, Jianwen, Qizhou Lian, Reida M. El Oakley, Bing Lim, and Sai-Kiang Lim. 2007. PI3 K/Akt/mTOR-mediated translational control regulates proliferation and differentiation of lineage-restricted RoSH stem cell lines. Journal of Molecular Signaling 2: 9.
AbstractBackground: We have previously derived highly similar lineage-restricted stem cell lines, RoSH and E-RoSH cell lines from mouse embryos and CD9hi SSEA-1- differentiated mouse embryonic stem cells, respectively. These cell lines are not pluripotent and differentiate readily into endothelial cells in vitro and in vivo. Results: We investigated the signaling pathway that maintains proliferation of these cells in an undifferentiated state, and demonstrate that PI3 K/Akt/mTOR, but not Raf/MEK/Erk, signaling in these cells was active during proliferation and was downregulated during endothelial differentiation. Inhibition of PI3 K/Akt/mTOR signaling, but not Raf/MEK/Erk, reduced proliferation and induced expression of endothelial specific proteins. During differentiation or inhibition of PI3 K/Akt/mTOR signaling, cyclinD2 transcript abundance in ribosome-enriched RNA but not in total RNA was reduced with a corresponding reduction in protein level. In contrast, transcript abundance of endothelial-specific genes e.g. Kdr, Tek and Pdgfrα in ribosome-enriched RNA fraction was not reduced and their protein levels were increased. Together these observations suggested that translational control mediated by PI3K/Akt/mTOR signaling was critical in regulating proliferation and endothelial differentiation of lineage-restricted RoSH-like stem cell lines. Conclusion: This study highlights translation regulation as a critical regulatory mechanism during proliferation and differentiation in stem cells.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4874785
- HMS Scholarly Articles