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000306695 1001_ $$00000-0001-6870-9938$$aPatra, Milan$$b0
000306695 245__ $$aSenescence of human pancreatic beta cells enhances functional maturation through chromatin reorganization and promotes interferon responsiveness.
000306695 260__ $$aOxford$$bOxford Univ. Press$$c2024
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000306695 520__ $$aSenescent 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.
000306695 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de
000306695 650_7 $$09008-11-1$$2NLM Chemicals$$aInterferons
000306695 650_7 $$2NLM Chemicals$$aInsulin
000306695 650_7 $$2NLM Chemicals$$aChromatin
000306695 650_7 $$2NLM Chemicals$$aCyclin-Dependent Kinase Inhibitor p16
000306695 650_2 $$2MeSH$$aHumans
000306695 650_2 $$2MeSH$$aInsulin-Secreting Cells: metabolism
000306695 650_2 $$2MeSH$$aCellular Senescence: genetics
000306695 650_2 $$2MeSH$$aChromatin Assembly and Disassembly
000306695 650_2 $$2MeSH$$aInterferons: metabolism
000306695 650_2 $$2MeSH$$aInterferons: genetics
000306695 650_2 $$2MeSH$$aInsulin Secretion
000306695 650_2 $$2MeSH$$aInsulin: metabolism
000306695 650_2 $$2MeSH$$aChromatin: metabolism
000306695 650_2 $$2MeSH$$aCyclin-Dependent Kinase Inhibitor p16: metabolism
000306695 650_2 $$2MeSH$$aCyclin-Dependent Kinase Inhibitor p16: genetics
000306695 650_2 $$2MeSH$$aCells, Cultured
000306695 650_2 $$2MeSH$$aSenescence-Associated Secretory Phenotype: genetics
000306695 650_2 $$2MeSH$$aTranscriptome
000306695 650_2 $$2MeSH$$aSingle-Cell Analysis
000306695 7001_ $$aKlochendler, Agnes$$b1
000306695 7001_ $$aCondiotti, Reba$$b2
000306695 7001_ $$aKaffe, Binyamin$$b3
000306695 7001_ $$aElgavish, Sharona$$b4
000306695 7001_ $$aDrawshy, Zeina$$b5
000306695 7001_ $$aAvrahami, Dana$$b6
000306695 7001_ $$00000-0001-7764-577X$$aNarita, Masashi$$b7
000306695 7001_ $$00000-0001-8368-0299$$aHofree, Matan$$b8
000306695 7001_ $$00000-0003-1725-2995$$aDrier, Yotam$$b9
000306695 7001_ $$00000-0003-4777-986X$$aMeshorer, Eran$$b10
000306695 7001_ $$00000-0003-2456-2289$$aDor, Yuval$$b11
000306695 7001_ $$00000-0001-7815-1165$$aBen-Porath, Ittai$$b12
000306695 773__ $$0PERI:(DE-600)1472175-2$$a10.1093/nar/gkae313$$gVol. 52, no. 11, p. 6298 - 6316$$n11$$p6298 - 6316$$tNucleic acids research$$v52$$x0305-1048$$y2024
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