转分化
再生(生物学)
体内
细胞生物学
高分辨率
生物
干细胞
计算生物学
地理
生物技术
遥感
作者
G. Liu,Yana Li,Mushan Li,Sheng Li,Qing He,S. Liu,Qiang Su,Xiangyi Chen,Minglu Xu,Zhenning Zhang,Zongshu Shao,Weida Li
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2023-05-24
卷期号:9 (21)
标识
DOI:10.1126/sciadv.adg2183
摘要
Adult mammals have limited capacity to regenerate functional cells. Promisingly, in vivo transdifferentiation heralds the possibility of regeneration by lineage reprogramming from other fully differentiated cells. However, the process of regeneration by in vivo transdifferentiation in mammals is poorly understood. Using pancreatic β cell regeneration as a paradigm, we performed a single-cell transcriptomic study of in vivo transdifferentiation from adult mouse acinar cells to induced β cells. Using unsupervised clustering analysis and lineage trajectory construction, we uncovered that the cell fate remodeling trajectory was linear at the initial stage and the reprogrammed cells either evolved to induced β cells or toward a “dead-end” state after day 4.Moreover, functional analyses identified both p53 and Dnmt3a that acted as reprogramming barriers during the process of in vivo transdifferentiation. Collectively, we decipher a high-resolution roadmap of regeneration by in vivo transdifferentiation and provide a detailed molecular blueprint to facilitate mammalian regeneration.
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