Mitochondrial fusion by pharmacological manipulation impedes somatic cell reprogramming to pluripotency: new insight into the role of mitophagy in cell stemness.

摘要: Recent studies have suggested a pivotal role for autophagy in stem cell maintenance and differentiation. Reprogramming of somatic cells to induced pluripotent (iPSCs) has been also bio-energetically take advantage mitochondrial (mitophagy). We preliminary addressed how mitophagy might play the regulation pluripotency using mdivi-1 (for division inhibitor), highly efficacious small molecule that selectively inhibits self-assembly DRP1, member dynamin family large GTPases mediates fission. At concentrations rapidly formation net-like or collapsed perinuclear structures, we observed reprogramming efficiency mouse embryonic fibroblasts transduced with Yamanaka three-factor cocktail (OCT4, KLF4, SOX2) is drastically reduced by more than 95%. Treatment MEFs at early stages before appearance iPSC colonies was sufficient completely inhibit reprogramming. Therefore, effects on efficiencies were due likely inhibition process itself not an impairment colony survival growth. Moreover, typical morphology established positive alkaline phosphatase staining negatively affected exposure. In presence mdivi-1, iPSCs lost, they somewhat resembled fibroblasts. The significantly reduced, finding indicative Our current findings provide new insight into integrated factors-driven transcriptional network specifies unique cells.