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Efficient stimulation of retinal regeneration from Müller glia in adult mice using combinations of proneural bHLH transcription factors.
- Source :
-
Cell reports [Cell Rep] 2021 Oct 19; Vol. 37 (3), pp. 109857. - Publication Year :
- 2021
-
Abstract
- Regenerative neuroscience aims to stimulate endogenous repair in the nervous system to replace neurons lost from degenerative diseases. Recently, we reported that overexpressing the transcription factor Ascl1 in Müller glia (MG) is sufficient to stimulate MG to regenerate functional neurons in the adult mouse retina. However, this process is inefficient, and only a third of the Ascl1-expressing MG generate new neurons. Here, we test whether proneural transcription factors of the Atoh1/7 class can further promote the regenerative capacity of MG. We find that the combination of Ascl1:Atoh1 is remarkably efficient at stimulating neurogenesis, even in the absence of retinal injury. Using electrophysiology and single-cell RNA sequencing (scRNA-seq), we demonstrate that Ascl1:Atoh1 generates a diversity of retinal neuron types, with the majority expressing characteristics of retinal ganglion cells. Our results provide a proof of principle that combinations of developmental transcription factors can substantially improve glial reprogramming to neurons and expand the repertoire of regenerated cell fates.<br />Competing Interests: Declaration of interests The University of Washington has applied for a patent incorporating technology partly described in this report with inventors L.T., T.A.R., and N.J. Research related to the findings in this report is currently being funded by Genentech in the lab of T.A.R. at the UW.<br /> (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Basic Helix-Loop-Helix Transcription Factors genetics
Cells, Cultured
Ependymoglial Cells pathology
Female
Gene Expression Regulation
Male
Mice, Inbred C57BL
Mice, Transgenic
Nerve Tissue Proteins genetics
Phenotype
RNA-Seq
Retina pathology
Signal Transduction
Single-Cell Analysis
Mice
Basic Helix-Loop-Helix Transcription Factors metabolism
Ependymoglial Cells metabolism
Nerve Regeneration
Nerve Tissue Proteins metabolism
Neurogenesis
Retina metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 37
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 34686336
- Full Text :
- https://doi.org/10.1016/j.celrep.2021.109857