Viral-mediated Pou5f1 (Oct4) overexpression and inhibition of Notch signaling synergistically induce neurogenic competence in mammalian Müller glia

• DOI: 10.7554/elife.106450
• Publication Date: 2025-04-02T15:07:07Z
• Authors: Nguyet Le; Sherine Awad; Isabella Palazzo; Thanh Hoang; Seth Blackshaw
• Keywords: Hes3 signaling axis

Retinal Müller glia in cold-blooded vertebrates can reprogram into neurogenic progenitors to replace neurons lost injury, but mammals lack this ability. While recent studies have shown that transgenic overexpression of bHLH factors and glial-specific disruption NFI family transcription Notch signaling induce competence mammalian glia, induction neurogenesis wildtype has thus far proven elusive. Here, we report viral-mediated the pluripotency factor Pou5f1 (Oct4) induces transdifferentiation mouse bipolar neurons, synergistically stimulates glial-derived parallel with loss function. Single-cell multiomic analysis shows leads widespread changes gene expression chromatin accessibility, inducing activity both Rfx4 Yamanaka Sox2 Klf4. This study demonstrates adult identifying mechanisms could be used cell-based therapies for treating retinal dystrophies.