生物
活性氧
线粒体ROS
细胞生物学
线粒体
GPX4
谷胱甘肽过氧化物酶
氧化应激
超氧化物歧化酶
生物化学
作者
Miao Zhang,Jingwei Sun,Xuan Huang,Song Bai,Min-Jiao Pang,Jiayi Li,Hanyu Chen,Qin Tong,Shi-Yu Ye,Xinyu Wang,Xu-Gang Hu,Jingying Li,Jin Zou,Wen Xu,Junhao Yang,Xi Liu,Jason C. Mills,Zhenning Wang
标识
DOI:10.1016/j.devcel.2024.03.002
摘要
In pyloric metaplasia, mature gastric chief cells reprogram via an evolutionarily conserved process termed paligenosis to re-enter the cell cycle and become spasmolytic polypeptide-expressing metaplasia (SPEM) cells. Here, we use single-cell RNA sequencing (scRNA-seq) following injury to the murine stomach to analyze mechanisms governing paligenosis at high resolution. Injury causes induced reactive oxygen species (ROS) with coordinated changes in mitochondrial activity and cellular metabolism, requiring the transcriptional mitochondrial regulator Ppargc1a (Pgc1α) and ROS regulator Nf2el2 (Nrf2). Loss of the ROS and mitochondrial control in Ppargc1a-/- mice causes the death of paligenotic cells through ferroptosis. Blocking the cystine transporter SLC7A11(xCT), which is critical in lipid radical detoxification through glutathione peroxidase 4 (GPX4), also increases ferroptosis. Finally, we show that PGC1α-mediated ROS and mitochondrial changes also underlie the paligenosis of pancreatic acinar cells. Altogether, the results detail how metabolic and mitochondrial changes are necessary for injury response, regeneration, and metaplasia in the stomach.
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