GSE208428
Reassessing in vivo conversion of Müller cells to retinal ganglion cells
The conversion of Müller cells (MGs) to retinal ganglion cells (RGCs) in vivo is a potential regeneration-based therapeutic strategy for optical nerve injury. It has been reported that Ptbp1 knockdown can efficiently convert MGs into RGCs. However, another study reported that mislabeling could have yielded a possible false positive. No previous studies have examined gene expression at single-cell resolution after Ptbp1 knockdown in MGs. Here, using CasRx-mediated knockdown of Ptbp1 in optic nerve crush model mice, we observed MG-to-RGC conversion in vivo and found that this conversion attenuated the symptoms of visual impairment caused by the loss of RGCs. ScRNA-seq revealed that a cluster of retinal progenitor cells (RPCs) underwent MG-to-RGC conversion after Ptbp1 knockdown. Our study confirmed the presence of intermediate cells during the MG-to-RGC conversion process after Ptbp1 knockdown and discovered transcription regulators including Nfix, Nfia, Crx, Rax, and Neurod1 are functionally involved in regulating this process. Overall design: Retinal mRNA profiles of  8 weeks after injection with AAV virus B6.Cg-Gt(ROSA)26Sortm9(CAG-tdTomato)Hze/J mice.