| First Author | Le N | Year | 2024 |
| Journal | Sci Adv | Volume | 10 |
| Issue | 28 | Pages | eadn2091 |
| PubMed ID | 38996013 | Mgi Jnum | J:351873 |
| Mgi Id | MGI:7665720 | Doi | 10.1126/sciadv.adn2091 |
| Citation | Le N, et al. (2024) Robust reprogramming of glia into neurons by inhibition of Notch signaling and nuclear factor I (NFI) factors in adult mammalian retina. Sci Adv 10(28):eadn2091 |
| abstractText | Generation of neurons through direct reprogramming has emerged as a promising therapeutic approach for treating neurodegenerative diseases. In this study, we present an efficient method for reprogramming retinal glial cells into neurons. By suppressing Notch signaling by disrupting either Rbpj or Notch1/2, we induced mature Muller glial cells to reprogram into bipolar- and amacrine-like neurons. We demonstrate that Rbpj directly activates both Notch effector genes and genes specific to mature Muller glia while indirectly repressing expression of neurogenic basic helix-loop-helix (bHLH) factors. Combined loss of function of Rbpj and Nfia/b/x resulted in conversion of nearly all Muller glia to neurons. Last, inducing Muller glial proliferation by overexpression of dominant-active Yap promotes neurogenesis in both Rbpj- and Nfia/b/x/Rbpj-deficient Muller glia. These findings demonstrate that Notch signaling and NFI factors act in parallel to inhibit neurogenic competence in mammalian Muller glia and help clarify potential strategies for regenerative therapies aimed at treating retinal dystrophies. |
