ArticleNucleic acids research2024
Senescence of human pancreatic beta cells enhances functional maturation through chromatin reorganization and promotes interferon responsiveness.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Article
- Article
- Proteostasis in the regulation of pancreatic islet cell plasticity.Journal of diabetes investigation · 2026Review
- SenFlag gene signature identifies senescent cells in mouse and human tissues through a conserved core transcriptional program.The EMBO journal · 2026Article
- Review
- Molecular mechanisms and recent advances in cellular senescence.Cell & bioscience · 2026Review
- Review
- iCLAP: an innovative method for integrable co-detection of low-abundance antigens with high-plex immunostaining.Nature communications · 2026Article
- Insulin production is sustained during DNA damage-mediated senescence in adult human beta cells.Diabetologia · 2026Article
- Interplay between aging and metabolic diseases: from molecular mechanisms to therapeutic horizons.Medical review (2021) · 2025Review
- Circulating senescence-associated secretory phenotype factors across the stages of type 1 diabetes in a cross-sectional cohort.Scientific reports · 2025Article
- Cells of all trades - on the importance of spatial positioning of senescent cells in development, healing and aging.FEBS letters · 2025Review
- Taurine Alleviates Pancreatic β-Cell Senescence by Inhibition of p53 Pathway.Journal of diabetes · 2025Article
- Pyruvate Carboxylase as a Moonlighting Metabolic Enzyme Protects β-Cell From Senescence.Journal of diabetes · 2025Article
- Comprehensive alpha, beta, and delta cell transcriptomics reveal an association of cellular aging with MHC class I upregulation.Molecular metabolism · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors.
Funding
Abstract
Senescent cells can influence the function of tissues in which they reside, and their propensity for disease. A portion of adult human pancreatic beta cells express the senescence marker p16, yet it is unclear whether they are in a senescent state, and how this affects insulin secretion. We analyzed single-cell transcriptome datasets of adult human beta cells, and found that p16-positive cells express senescence gene signatures, as well as elevated levels of beta-cell maturation genes, consistent with enhanced functionality. Senescent human beta-like cells in culture undergo chromatin reorganization that leads to activation of enhancers regulating functional maturation genes and acquisition of glucose-stimulated insulin secretion capacity. Strikingly, Interferon-stimulated genes are elevated in senescent human beta cells, but genes encoding senescence-associated secretory phenotype (SASP) cytokines are not. Senescent beta cells in culture and in human tissue show elevated levels of cytoplasmic DNA, contributing to their increased interferon responsiveness. Human beta-cell senescence thus involves chromatin-driven upregulation of a functional-maturation program, and increased responsiveness of interferon-stimulated genes, changes that could increase both insulin secretion and immune reactivity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.