ASCL1 induces neurogenesis in human Müller glia.


Journal

Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300

Informations de publication

Date de publication:
12 Dec 2023
Historique:
received: 22 03 2023
revised: 27 10 2023
accepted: 30 10 2023
pubmed: 2 12 2023
medline: 2 12 2023
entrez: 1 12 2023
Statut: ppublish

Résumé

In mammals, loss of retinal cells due to disease or trauma is an irreversible process that can lead to blindness. Interestingly, regeneration of retinal neurons is a well established process in some non-mammalian vertebrates and is driven by the Müller glia (MG), which are able to re-enter the cell cycle and reprogram into neurogenic progenitors upon retinal injury or disease. Progress has been made to restore this mechanism in mammals to promote retinal regeneration: MG can be stimulated to generate new neurons in vivo in the adult mouse retina after the over-expression of the pro-neural transcription factor Ascl1. In this study, we applied the same strategy to reprogram human MG derived from fetal retina and retinal organoids into neurons. Combining single cell RNA sequencing, single cell ATAC sequencing, immunofluorescence, and electrophysiology we demonstrate that human MG can be reprogrammed into neurogenic cells in vitro.

Identifiants

pubmed: 38039971
pii: S2213-6711(23)00423-X
doi: 10.1016/j.stemcr.2023.10.021
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2400-2417

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests This research is funded in part by a sponsored research agreement with Tenpoint Therapeutics; T.A.R. is a co-founder and consultant. Some of the findings in this manuscript are part of a patent that has been submitted by the University of Washington: PCT/US23/65219.

Auteurs

Juliette Wohlschlegel (J)

Department of Biological Structure, University of Washington, Seattle, WA, USA.

Connor Finkbeiner (C)

Department of Biological Structure, University of Washington, Seattle, WA, USA.

Dawn Hoffer (D)

Department of Biological Structure, University of Washington, Seattle, WA, USA.

Faith Kierney (F)

Department of Biological Structure, University of Washington, Seattle, WA, USA.

Aric Prieve (A)

Department of Biological Structure, University of Washington, Seattle, WA, USA.

Alexandria D Murry (AD)

Department of Biological Structure, University of Washington, Seattle, WA, USA.

Alexandra K Haugan (AK)

Department of Biological Structure, University of Washington, Seattle, WA, USA.

Isabel Ortuño-Lizarán (I)

Department of Biological Structure, University of Washington, Seattle, WA, USA.

Fred Rieke (F)

Department of Physiology and Biophysics, University of Washington, Seattle, WA, USA.

Sam A Golden (SA)

Department of Biological Structure, University of Washington, Seattle, WA, USA; Center of Excellence in Neurobiology of Addiction, Pain, and Emotion (NAPE), University of Washington, Seattle, WA, USA.

Thomas A Reh (TA)

Department of Biological Structure, University of Washington, Seattle, WA, USA; Institute for Stem Cells and Regenerative Medicine, University of Washington, Seattle, WA, USA. Electronic address: tomreh@uw.edu.

Classifications MeSH