Robust Reprogramming of Glia into Neurons by Inhibition of Notch Signaling and Nuclear Factor I (NFI) Factors in Adult Mammalian Retina

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2024 Jul 12

PMID 38996013

Authors

Nguyet Le

Trieu-Duc Vu

Isabella Palazzo

Ritvik Pulya

Yehna Kim

Seth Blackshaw

Thanh Hoang

Affiliations

Soon will be listed here.

Abstract

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 or , we induced mature Müller 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 Müller glia while indirectly repressing expression of neurogenic basic helix-loop-helix (bHLH) factors. Combined loss of function of and resulted in conversion of nearly all Müller glia to neurons. Last, inducing Müller glial proliferation by overexpression of dominant-active Yap promotes neurogenesis in both - and -deficient Müller glia. These findings demonstrate that Notch signaling and NFI factors act in parallel to inhibit neurogenic competence in mammalian Müller glia and help clarify potential strategies for regenerative therapies aimed at treating retinal dystrophies.

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