Plagl2 unlocks the latent reprogramming potential of adult mouse Muller glia
MÃ¼ller glia (MG) in the adult mammalian retina have long been recognized as a potential endogenous source for regenerating lost retinal neurons. However, existing MG reprogramming strategies yield an incomplete regenerative response by favoring either proliferation or neurogenic conversion. Here, we show that the zinc-finger transcription factor Plagl2, which was previously identified as a rejuvenator of aged neural stem cells, sufficiently reprograms adult mouse MG into a bona fide retinal progenitor cell-like state with coupled proliferative and neurogenic competence. Using histology, time-lapse imaging, and single-cell transcriptomics, we demonstrate that Plagl2 drives regulated rounds of MG cell cycle re-entry, while N-methyl-D-aspartate-induced retinal injury further promotes the acquisition of neurogenic competence toward inner nuclear layer neuronal identities. These findings highlight Plagl2 as a novel MG rejuvenator and support a general principle that reprogramming modules may be redeployed across cell types, offering new avenues for unlocking regenerative potential in otherwise non-regenerative tissues.