机构：[1]State Key Laboratory ofMembrane Biology,Institute of Zoology,Chinese Academy ofSciences, Beijing 100101,China[2]Beijing AdvancedInnovation Center forGenomics, BiomedicalPioneering InnovationCenter, College of LifeSciences, PekingUniversity, Beijing100871, China[3]StateKey Laboratory of StemCell and ReproductiveBiology, Institute ofZoology, ChineseAcademy of Sciences,Beijing 100101, China[4]National Laboratory ofBiomacromolecules, CASCenter for Excellence inBiomacromolecules,Institute of Biophysics,Chinese Academy ofSciences, Beijing 100101,China[5]Beijing Institutefor Brain Disorders,Advanced InnovationCenter for Human BrainProtection, NationalClinical Research Centerfor Geriatric Disorders,Xuanwu Hospital CapitalMedical University,Beijing 100053, China首都医科大学宣武医院[6]University of ChineseAcademy of Sciences,Beijing 100049, China[7]Institute for Stem Celland Regeneration,Chinese Academy ofSciences, Beijing 100101,China[8]Ministry ofEducation Key Laboratoryof Cell Proliferation andDifferentiation, Beijing100871, China[9]Peking-Tsinghua Centerfor Life Sciences,Academy for AdvancedInterdisciplinary Studies,Peking University, Beijing100871, China[10]GeneExpression Laboratory,Salk Institute forBiological Studies, LaJolla, CA 92037, USA[11]CAS Key Laboratory ofGenomic and PrecisionMedicine, BeijingInstitute of Genomics,Chinese Academy ofSciences, Beijing 100101,China[12]China NationalCenter forBioinformation, Beijing100101, China and 13TheMOH Key Laboratory ofGeriatrics, BeijingHospital, National Centerof Gerontology, Beijing100730, China
Aging-related degeneration of pancreatic islet cells contributes to impaired glucose tolerance and diabetes. Endocrine cells age heterogeneously, complicating the efforts to unravel the molecular drivers underlying endocrine aging. To overcome these obstacles, we undertook single-cell RNA sequencing of pancreatic islet cells obtained from young and aged non-diabetic cynomolgus monkeys. Despite sex differences and increased transcriptional variations, aged beta-cells showed increased unfolded protein response (UPR) along with the accumulation of protein aggregates. We observed transcriptomic dysregulation of UPR components linked to canonical ATF6 and IRE1 signaling pathways, comprising adaptive UPR during pancreatic aging. Notably, we found aging-related beta-cell-specific upregulation of HSP90B1, an endoplasmic reticulum-located chaperone, impeded high glucose-induced insulin secretion. Our work decodes aging-associated transcriptomic changes that underlie pancreatic islet functional decay at single-cell resolution and indicates that targeting UPR components may prevent loss of proteostasis, suggesting an avenue to delaying beta-cell aging and preventing aging-related diabetes.
基金：
National Key Research and Development Program of China [2018YFC2000100, 2017YFA0102802, 2017YFA0103304, 2018YFA0107203, 2018YFC2000400]; Strategic Priority Research Program of the Chinese Academy of SciencesChinese Academy of Sciences [XDA16010100]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81625009, 91749202, 81861168034, 81921006, 31671429, 91949209, 91749123, 81671377, 91849132, 81822018, 81870228, 81922027, 81701388, 81801399]; Program of the Beijing Municipal Science and Technology Commission [Z191100001519005]; Beijing Natural Science FoundationBeijing Natural Science Foundation [Z190019]; Beijing Municipal Commission of Health and Family Planning [PXM2018 026283 000002]; Advanced Innovation Center for Human Brain Protection [3500-1192012]; Key Research Program of the Chinese Academy of SciencesChinese Academy of Sciences [KFZD-SW-221]; K.C. Wong Education Foundation [GJTD-2019-06, GJTD2019-08]; Young Elite Scientists Sponsorship Program by CAST [2017QNRC001]; Youth Innovation Promotion Association of CAS; State Key Laboratory of Stem Cell and Reproductive Biology; State Key Laboratory of Membrane Biology; Glenn Foundation; Diabetes Research Connection
第一作者机构：[1]State Key Laboratory ofMembrane Biology,Institute of Zoology,Chinese Academy ofSciences, Beijing 100101,China[4]National Laboratory ofBiomacromolecules, CASCenter for Excellence inBiomacromolecules,Institute of Biophysics,Chinese Academy ofSciences, Beijing 100101,China[5]Beijing Institutefor Brain Disorders,Advanced InnovationCenter for Human BrainProtection, NationalClinical Research Centerfor Geriatric Disorders,Xuanwu Hospital CapitalMedical University,Beijing 100053, China[6]University of ChineseAcademy of Sciences,Beijing 100049, China
共同第一作者：
通讯作者：
通讯机构：[1]State Key Laboratory ofMembrane Biology,Institute of Zoology,Chinese Academy ofSciences, Beijing 100101,China[2]Beijing AdvancedInnovation Center forGenomics, BiomedicalPioneering InnovationCenter, College of LifeSciences, PekingUniversity, Beijing100871, China[3]StateKey Laboratory of StemCell and ReproductiveBiology, Institute ofZoology, ChineseAcademy of Sciences,Beijing 100101, China[4]National Laboratory ofBiomacromolecules, CASCenter for Excellence inBiomacromolecules,Institute of Biophysics,Chinese Academy ofSciences, Beijing 100101,China[5]Beijing Institutefor Brain Disorders,Advanced InnovationCenter for Human BrainProtection, NationalClinical Research Centerfor Geriatric Disorders,Xuanwu Hospital CapitalMedical University,Beijing 100053, China[6]University of ChineseAcademy of Sciences,Beijing 100049, China[7]Institute for Stem Celland Regeneration,Chinese Academy ofSciences, Beijing 100101,China[8]Ministry ofEducation Key Laboratoryof Cell Proliferation andDifferentiation, Beijing100871, China[9]Peking-Tsinghua Centerfor Life Sciences,Academy for AdvancedInterdisciplinary Studies,Peking University, Beijing100871, China[11]CAS Key Laboratory ofGenomic and PrecisionMedicine, BeijingInstitute of Genomics,Chinese Academy ofSciences, Beijing 100101,China[12]China NationalCenter forBioinformation, Beijing100101, China and 13TheMOH Key Laboratory ofGeriatrics, BeijingHospital, National Centerof Gerontology, Beijing100730, China
推荐引用方式(GB/T 7714)：
Li Jingyi,Zheng Yuxuan,Yan Pengze,et al.A single-cell transcriptomic atlas of primate pancreatic islet aging[J].NATIONAL SCIENCE REVIEW.2021,8(2):doi:10.1093/nsr/nwaa127.
综合性期刊