Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
CAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
FASEB J. 2020 Mar;34(3):4764-4782. doi: 10.1096/fj.201902118R. Epub 2020 Feb 6.
Damage or degeneration of inner ear spiral ganglion neurons (SGNs) causes hearing impairment. Previous in vitro studies indicate that cochlear glial cells can be reprogrammed into SGNs, however, it remains unknown whether this can occur in vivo. Here, we show that neonatal glial cells can be converted, in vivo, into SGNs (defined as new SGNs) by simultaneous induction of Neurog1 (Ngn1) and Neurod1. New SGNs express SGN markers, Tuj1, Map2, Prox1, Mafb and Gata3, and reduce glial cell marker Sox10 and Scn7a. The heterogeneity within new SGNs is illustrated by immunostaining and transcriptomic assays. Transcriptomes analysis indicates that well reprogrammed SGNs are similar to type I SGNs. In addition, reprogramming efficiency is positively correlated with the dosage of Ngn1 and Neurod1, but declined with aging. Taken together, our in vivo data demonstrates the plasticity of cochlear neonatal glial cells and the capacity of Ngn1 and Neurod1 to reprogram glial cells into SGNs. Looking ahead, we expect that combination of Neurog1 and Neurod1 along with other factors will further boost the percentage of fully converted (Mafb+/Gata3+) new SGNs.
内耳螺旋神经节神经元（SGNs）的损伤或退化导致听力受损。以前的体外研究表明，耳蜗神经胶质细胞可以被重编程为 SGNs，但尚不清楚这是否可以在体内发生。在这里，我们表明，通过同时诱导 Neurog1（Ngn1）和 Neurod1，新生的神经胶质细胞可以在体内转化为 SGNs（定义为新的 SGNs）。新的 SGNs 表达 SGN 标记物，如 Tuj1、Map2、Prox1、Mafb 和 Gata3，并减少神经胶质细胞标记物 Sox10 和 Scn7a。通过免疫染色和转录组分析说明了新 SGN 内的异质性。转录组分析表明，经过良好重编程的 SGNs 与 I 型 SGNs 相似。此外，重编程效率与 Ngn1 和 Neurod1 的剂量呈正相关，但随年龄增长而下降。总之，我们的体内数据表明耳蜗新生神经胶质细胞具有可塑性，并且 Ngn1 和 Neurod1 能够将神经胶质细胞重编程为 SGNs。展望未来，我们预计 Neurog1 和 Neurod1 与其他因素的结合将进一步提高完全转化（Mafb+/Gata3+）的新 SGN 的比例。
