MAPK14 Governs Mammalian Müller glia Fate Determination between Gliosis and Reprogramming

Irreversible loss of retinal neurons is the leading cause of blindness. Harnessing the latent stem cell potential of mammalian Müller glia offers a promising strategy for endogenous retinal regeneration. Shifting the Müller glia response from gliosis to regeneration after retinal injury is a critical step in promoting the orderly entry of Müller glia into a regenerative program. However, the molecular switch governing this divergent fate decision remains elusive. Here, through RNA-seq and scRNA-seq, we confirm the upstream determinant of Müller glia fate after retinal injury. Overall design: RNA sequencing was performed on MIO-M1 cells following MAPK14 or control siRNA treatment, as well as MAPK8+9 or control siRNA treatment, according to the manufacturer's instructions, to identify downstream signaling changes. To characterize the types of neurons regenerated in Adezmapimod-treated mice, we performed scRNA-seq) on fluorescence-activated cell sorting (FACS)-purified MG and their neuronal progeny 1 month after NMDA and Adezmapimod treatment.