Reprogramming lineage-traced Müller glia for robust proliferation and neurogenesis in adult mammalian retinas

In cold-blooded vertebrates such as zebrafish, Müller glia (MG) act as endogenous retinal stem/progenitor cells upon retinal injury, which evokes a regenerative response that proceeds first with an symmetric division to generate a MG-derived multipotent progenitor cell robust proliferation of MG-derived multipotent progenitors (MGPCs) through that undergoes multiple rounds of cell division, followed by differentiation of MGPCs into new retinal neurons.

By contrast, mammalian MG undergo reactive gliosis following retinal injury rather than cell-cycle re-entry for proliferation, hindering its capacity to replenish the lost retinal neuronal cells under pathological conditions. In this study, we treat the adult mouse retina with the combination of FGF2 (Fibroblast growth factor 2) and RA (retinoic acid) after AAV-mediated MG-specific gene transfer of Ascl1 (FAR), and scRNA-seq was employed to see whether the FAR treatment could induced robust MG proliferation and neural regeneration in adult mouse retina.