Increasing cell culture density during a developmental window prevents fated rod precursors derailment toward hybrid rod-glia cells.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
13 04 2023
13 04 2023
Historique:
received:
09
11
2022
accepted:
29
03
2023
medline:
17
4
2023
entrez:
13
4
2023
pubmed:
14
4
2023
Statut:
epublish
Résumé
In proliferating multipotent retinal progenitors, transcription factors dynamics set the fate of postmitotic daughter cells, but postmitotic cell fate plasticity driven by extrinsic factors remains controversial. Transcriptome analysis reveals the concurrent expression by postmitotic rod precursors of genes critical for the Müller glia cell fate, which are rarely generated from terminally-dividing progenitors as a pair with rod precursors. By combining gene expression and functional characterisation in single cultured rod precursors, we identified a time-restricted window where increasing cell culture density switches off the expression of genes critical for Müller glial cells. Intriguingly, rod precursors in low cell culture density maintain the expression of genes of rod and glial cell fate and develop a mixed rod/Muller glial cells electrophysiological fingerprint, revealing rods derailment toward a hybrid rod-glial phenotype. The notion of cell culture density as an extrinsic factor critical for preventing rod-fated cells diversion toward a hybrid cell state may explain the occurrence of hybrid rod/MG cells in the adult retina and provide a strategy to improve engraftment yield in regenerative approaches to retinal degenerative disease by stabilising the fate of grafted rod precursors.
Identifiants
pubmed: 37055439
doi: 10.1038/s41598-023-32571-y
pii: 10.1038/s41598-023-32571-y
pmc: PMC10101963
doi:
Substances chimiques
Transcription Factors
0
Banques de données
figshare
['10.6084/m9.figshare.21333972.v3']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6025Informations de copyright
© 2023. The Author(s).
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