逆生:完全分化细胞可塑性在再生与肿瘤发生中的双重角色OA

Paligenos is the process through which fully differentiated,mature cells reversibly revert to a progenitor-like state via endoge-nous programs thereby contributing to the repair of damaged tissues.This process is comprised of three key stages:activation of autophagy by inhibiting mammalian target of rapamycin complex 1(mTORC1)signaling,which leads to degradation differentiation-specific struc-tures;release from the differentiated state and activation of stem cell-related genes(SOX9 and LGR5);restarting the cell cycle to achieve functional proliferation.Among these stages,the inhibition and subsequent reactivation of mTORC1 is the core regulatory mechanism,responsible for coordinating autophagy,metabolic reprogramming,and genomic surveillance.Paligenosis has dual physiological and patho-logical roles.Various cells,including gastric chief cells and pancreatic acinar cells,participate in damage repair through paligenosis,but its abnormal activation can lead to intestinal metaplasia and an increased risk of carcinogenesis.Furthermore,in tumorigenesis,paligenosis drives mutation accumulation,challenging the"cancer stem cell"theoretical framework to enable differentiated cells to directly participate in tumor origin,thereby mediating drug resistance and metastasis via phenotypic plasticity.This study provides insights into the molecular mechanism of paligenosis,its mode of action in tissue repair,and its association with tumorigenesis,thereby revealing its dual roles in health and disease and informing future research.