Suppression Of Ataxia Telangiectasia Mutated Promotes Somatic Cells Reprogramme To IPS Cells

The process of somatic cells reprogramming underwent a wide range of chromatin remodeling,which is accompanied by a large amount of DNA damage,further affected the efficiency of reprogramming.However,the regulation mechanism of DNA damage in this process is still unclear.Recently,the mechanism that ataxia telangiectasia mutated(ATM),a key regulator in DNA damage affected somatic reprogramming was investigated.It provided insights to understand the mechanism of somatic cell reprogramming.The results showed that KU-60019,a inhibitor of ATM contained in the medium at reprogramming PD2-PD4,significantly improved generation of iPS cells.The iPS cells had normal pluripotency.Subsequently,ATM inhibition up-regulated or down-regulated autophagy-related genes such as Atg3,Atg5,Tsc1,Tsc2 and glucose metabolism-related genes Akt1,but autophagy marker LC3 and AKTprotein were not change.ATM inhibition also inhibited activation of?H2AX.Although ATM inhibition did not affect expression of 53BP1 and Chk2 proteins,expression of Brca1,Brca2 and Nbs1 genes that involved in DNA homologous recombination repair were down-regulated.Further,Although ATM inhibition did not affect P19,a upstream protein of P53 signal pathway,p53 was inhibited.KU-60019 treatment significantly decreased cellular senescence,but not affected apoptosis during reprogramming.Finally,ATM is a key factor in identifying DNA damage during reprogramming,which inhibits somatic cell reprogramming through its downstream H2 AX and p53 signaling pathways by activating cellular aging.