EpiCRISPR targeted methylation of Arx gene initiates transient switch of mouse pancreatic alpha to insulin-producing cells.
Arx gene
CRISPR/dCas9
diabetes
epigenetic editing
pancreatic alpha cells
targeted DNA methylation
Journal
Frontiers in endocrinology
ISSN: 1664-2392
Titre abrégé: Front Endocrinol (Lausanne)
Pays: Switzerland
ID NLM: 101555782
Informations de publication
Date de publication:
2023
2023
Historique:
received:
30
12
2022
accepted:
24
02
2023
medline:
4
4
2023
entrez:
3
4
2023
pubmed:
4
4
2023
Statut:
epublish
Résumé
Beta cell dysfunction by loss of beta cell identity, dedifferentiation, and the presence of polyhormonal cells are main characteristics of diabetes. The straightforward strategy for curing diabetes implies reestablishment of pancreatic beta cell function by beta cell replacement therapy. Aristaless-related homeobox (Arx) gene encodes protein which plays an important role in the development of pancreatic alpha cells and is a main target for changing alpha cell identity. In this study we used CRISPR/dCas9-based epigenetic tools for targeted hypermethylation of Arx gene promoter and its subsequent suppression in mouse pancreatic αTC1-6 cell line. Bisulfite sequencing and methylation profiling revealed that the dCas9-Dnmt3a3L-KRAB single chain fusion constructs (EpiCRISPR) was the most efficient. Epigenetic silencing of In conclusion, we successfully triggered a direct, transient switch of pancreatic alpha to insulin-producing cells opening a future research on promising therapeutic avenue for diabetes management.
Identifiants
pubmed: 37008919
doi: 10.3389/fendo.2023.1134478
pmc: PMC10063207
doi:
Substances chimiques
Transcription Factors
0
Homeodomain Proteins
0
Insulin
0
ARX protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1134478Informations de copyright
Copyright © 2023 Đorđević, Stepper, Feuerstein-Akgoz, Gerhauser, Paunović, Tolić, Rajić, Dinić, Uskoković, Grdović, Mihailović, Jurkowska, Jurkowski, Jovanović and Vidaković.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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