Abstract
Background aims. The identification of mesenchymal stromal cells (MSC) from bone marrow by Friedenstein et al. dates back to 1970, but many questions remain unanswered about the biology of these cells. MSC have a wide clinical application because of their differentiation capacity and immunosuppressive properties. They are capable of self-renewal; however, the mechanism is poorly understood. The embryonic transcription factor Octamer binding transcription factor 4 (Oct4) has been suggested as an indicator of multipotency for mouse MSC. OCT4 has also been studied extensively for its involvement in self-renewal of embryonic stem cells and in cancer cells. Methods. Using a lentiviral-inducible vector, we modulated OCT4 expression in human MSC and studied its effect on the biology of these cells. Results. Surprisingly, we found that the overexpression of OCT4 induced early senescence, as evidenced by increased expression of P14 and P16INK4A in MSC. Conclusions. These results indicate a differential role for exogenously expressed human OCT4 in adult and embryonic systems.
Acknowledgments
We thank Dr Fernando Anjos Afonso for providing the p14 and p21 primers, Dr Goedele Maertens for the p16INK4A primers, and Lola Martinez for help with the TMRE analysis. This work was funded by Cancer Research UK and a European grant (contract number LHSB-CT-2006–018817) to DB. BGJ is currently affiliated with Department of Biotechnology, Indian Institute of Technology, Guwahati, Assam, India.
Author contribution: BGJ designed and performed the research, analyzed the data and wrote the manuscript; DB designed the research, analyzed and interpreted the data and wrote the manuscript.
Conflict of interest statement: The authors declare no competing financial interests.