Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
Tsingtao Advanced Research Institute, Tongji University, Qingdao 266073, China.
Sci Adv. 2023 May 24;9(21):eadg2183. doi: 10.1126/sciadv.adg2183.
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 and 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.
成年哺乳动物的功能细胞再生能力有限。有研究表明，体内转分化预示着通过谱系重编程，由其他完全分化的细胞实现再生的可能性。然而，哺乳动物体内转分化的再生过程尚不清楚。本文以胰腺β细胞再生为例，对成年鼠腺泡细胞向诱导β细胞的体内转分化进行了单细胞转录组学研究。通过无监督聚类分析和谱系轨迹构建，揭示了细胞命运重塑轨迹在初始阶段呈线性，重编程细胞要么在第 4 天前向诱导β细胞进化，要么向“死胡同”状态进化。此外，功能分析确定了 和 作为体内转分化过程中的重编程障碍。总之，本文揭示了体内转分化的高分辨率再生路线图，并提供了详细的分子蓝图，以促进哺乳动物的再生。
