In mammals, loss of retinal cells due to disease or trauma is an irreversible process that can lead to blindness. Interestingly, regeneration of retinal neurons is a well established process in some non-mammalian vertebrates and is driven by the Müller glia (MG), which are able to re-enter the cell cycle and reprogram into neurogenic progenitors upon retinal injury or disease. Progress has been made to restore this mechanism in mammals to promote retinal regeneration: MG can be stimulated to generate new neurons in vivo in the adult mouse retina after the over-expression of the pro-neural transcription factor Ascl1. In this study, we applied the same strategy to reprogram human MG derived from fetal retina and retinal organoids into neurons. Combining single cell RNA sequencing, single cell ATAC sequencing, immunofluorescence, and electrophysiology we demonstrate that human MG can be reprogrammed into neurogenic cells in vitro.

在哺乳动物中，由于疾病或创伤而导致的视网膜细胞损失是一个不可逆转的过程，可能导致失明。有趣的是，视网膜神经元的再生在一些非哺乳动物脊椎动物中是一个成熟的过程，由穆勒神经胶质细胞（MG）驱动，在视网膜损伤或疾病时，MG能够重新进入细胞周期并重新编程为神经祖细胞。在哺乳动物中恢复这种促进视网膜再生的机制已经取得了进展：在前神经转录因子Ascl1过度表达后，可以刺激 MG 在成年小鼠视网膜体内产生新的神经元。在这项研究中，我们应用相同的策略将源自胎儿视网膜和视网膜类器官的人类 MG 重新编程为神经元。结合单细胞 RNA 测序、单细胞 ATAC 测序、免疫荧光和电生理学，我们证明人类 MG 可以在体外重编程为神经源性细胞。