Page 20 - X. Stem cell biology

[X. Stem cell biology-12]

Oct-4, Sox2, Klf-4, and c-Myc Reprogramming Factors Delay

Premature Senescence through the Activation of Cyclin D1

Jung hoon Kim¹, Jung ho Kim¹˙*

¹Laboratory of Molecular and Cellular Biology, Department of Life Science, Sogang University, Seoul 04107, Korea

Although pluripotent stem cells hold great promise in the fields of human disease modeling and regenerative
medicine, the molecular basis of Oct-4, Sox2, Klf4, and c-Myc -induced cellular reprogramming remains unclear. To
investigate the molecular mechanisms involved in cellular reprogramming, we studied the immediate effects of

expression of the reprogramming factors on mouse embryonic fibroblasts in this study. Although MEFs not

expressing the reprogramming factors underwent replicative senescence within 9–12 days, MEFs expressing the four
reprogramming factors proliferated continuously throughout the duration of the experiment. Cell cycle progression
by the reprogramming factors was accompanied by accumulation of Cyclin D1 through the early stages of

reprogramming in MEFs. Forced Cyclin D1 expression enhanced reprogramming if administered concomitant with
expression of the OSKM reprogramming factors. expressing reprogramming factors. the number of emerging AP-

positive cyclin D1-/- colonies was significantly reduced and cyclin D1-/- MEFs were unable to initiate mesenchymal-
to-epithelial transition, compared to wild type MEFs expressing reprogramming factors. Our studies demonstrate

that activation of cyclin D1 by reprogramming factors is an important process for reprogramming.