Research article

PI3 K/Akt/mTOR-mediated translational control regulates proliferation and differentiation of lineage-restricted RoSH stem cell lines

Jianwen Que¹ , Qizhou Lian¹ , Reida M El Oakley¹ , Bing Lim^2,3 and Sai-Kiang Lim⁴

¹Dept. of Surgery, National University of Singapore, Lower Kent Ridge Road, Singapore 117597

²Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672

³Beth Israel Deaconess Medical Center, Harvard Medical School, 4 Blackfan Circle, Boston, MA, USA 02115

⁴Institute of Medical Biology, 11 Biopolis Street, Helios #02-02, Singapore 13866

author email corresponding author email

Journal of Molecular Signaling 2007, 2:9doi:10.1186/1750-2187-2-9

Published:	25 September 2007

Abstract

Background

We have previously derived highly similar lineage-restricted stem cell lines, RoSH and E-RoSH cell lines from mouse embryos and CD9^hi 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.