Role And Mechanism Of Autophagy In Somatic Cell Reprogramming

Reprogramming of somatic cells into induced pluripotent stem cells by defined transcription factors remains poorly understood at the celluar level. In the early stage of reprogramming, cells go through mesenchymal-to-epithelial transition (MET) and proliferate faster. The metabolic switch from aerobic oxidative phosphorylation to anerobic glycolysis happens. Epigenetics changes greatly in genome wide. Additionally, cell size shrinks, along with decrease of organelles, including mitochondria, endoplasmic reticulum and Golgi complex. These intracellular changes indicate that cells remodel the cytoplasmic components in early reprogramming. Autophagy is a stress-induced degradation process to eliminate proteins and organelles to help cells to survive. We hypothesized that autophagy might participate in early reprogramming.In this study we found that,1, autophagy is induced in early reprogramming;2, c-Myc and Klf4activate autophagy independent of p53;3, autophagy induction restrains reprogramming;4, autophagy repress reprogramming efficiency by degrading midbody;5, autophagy repressor mTORC1plays dual roles in reprogramming. Thus, we identified autophagy as a new barrier for reprogramming.And we found that the autophagy receptor P62accumulates in Atg5knockout cells. We are now exploring whether p62regulates reprogramming.