Heterogeneous enhancer states orchestrate β cell responses to metabolic stress.
Animals
Insulin-Secreting Cells
/ metabolism
Mice
Enhancer Elements, Genetic
/ genetics
Stress, Physiological
/ genetics
Hepatocyte Nuclear Factor 3-beta
/ metabolism
Obesity
/ metabolism
Histones
/ metabolism
Endoplasmic Reticulum Stress
/ genetics
Mice, Inbred C57BL
Nerve Growth Factor
/ metabolism
Male
Single-Cell Analysis
Diabetes Mellitus, Type 2
/ metabolism
Paracrine Communication
Cell Communication
Mice, Obese
Epigenesis, Genetic
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
30 Oct 2024
30 Oct 2024
Historique:
received:
23
10
2023
accepted:
18
10
2024
medline:
30
10
2024
pubmed:
30
10
2024
entrez:
30
10
2024
Statut:
epublish
Résumé
Obesity-induced β cell dysfunction contributes to the onset of type 2 diabetes. Nevertheless, elucidating epigenetic mechanisms underlying islet dysfunction at single cell level remains challenging. Here we profile single-nuclei RNA along with enhancer marks H3K4me1 or H3K27ac in islets from lean or obese mice. Our study identifies distinct gene signatures and enhancer states correlating with β cell dysfunction trajectory. Intriguingly, while many metabolic stress-induced genes exhibit concordant changes in both H3K4me1 and H3K27ac at their enhancers, expression changes of specific subsets are solely attributable to either H3K4me1 or H3K27ac dynamics. Remarkably, a subset of H3K4me1
Identifiants
pubmed: 39472434
doi: 10.1038/s41467-024-53717-0
pii: 10.1038/s41467-024-53717-0
doi:
Substances chimiques
Hepatocyte Nuclear Factor 3-beta
135845-92-0
Histones
0
Nerve Growth Factor
9061-61-4
Foxa2 protein, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9361Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK132651
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK120808
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002377
Pays : United States
Informations de copyright
© 2024. The Author(s).
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