The Regulation Pathway Of Mitochondrial Permeability Transition Pore On Early Somatic Cells Reprogramming

Induced pluripotent stem cells and ES cells have many similar characteristics,it can be obtained by transferred four factors SKOM(Sox2,Klf4,Oct4,c-Myc)into somatic cells.And it has unlimited application in regenerative medicine and emerging cell therapy.As there is a big difference between somatic cells and stem cells in mitochondrial morphology and function,The mitochondria also undergo significant changes during reprogramming,So we want to know how mitochondria and nucleus regulate each other?In this study we found that a pore called mitochondrial permeability transition pore(mPTP)is very different between ES cells and somatic cells by confocal imaging technology,The mPTP of ES cells is fully opening while in somatic cells MEFs it is closing,The reprogramming process was also accompanying with the changing of mPTP from closing to opening,This suggests that mPTP opening is a must phenomenon for reprogramming process,Based on this we examined the effect of mPTP on reprogramming.By over expression of CypD,a protein that regulates the opening of mPTP,we found that it can only improve the efficiency of reprogramming at an early stage,The further research has revealed that the mechanism is not causing by MET changing or DNA damage responses,But having a relationship with changing in the reduction of H3K9 methylation and H3K27 methylation,By using CHIP-qPCR,We also found that the above modification has reduced in pluripotency gene,And it promotes the expression of Nanog.We further pointed that these changings were mediated by a demethylase named PHF8 through Western blot and RNA interference.So we initially identified a signal pathway that mPTP can change the modifications of histone through PHF8.Besides,We also induced the expression of PHF8 during the MEF reprogramming,We found that it's function and efficiency can not consist with CypD expression.So the mechanism of mPTP on reprogramming need to be further studied.The purpose of our experiments is to better solve the series of complex regulation during the reprogramming process,And also to further study the regulation of signal pathways based on the platform of reprogramming,which ultimately make iPSCs better and safer applied to the clinical treatment.