e.g. IL6;  SIRT6; 

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National Science Review. 2020.

A Single-cell Transcriptomic Atlas of Primate Pancreatic Islet Aging

Jingyi Li 1 4 5 6 , Yuxuan Zheng 2 8 9 , Pengze Yan 1 6 , Moshi Song 1 6 7 , Si Wang 1 5 6 7 , Liang Sun 13 , Zunpeng Liu 3 6 , Shuai Ma 1 6 7 , Juan Carlos Izpisua Belmonte 10 , Piu Chan 5 , Qi Zhou 3 6 7 , Weiqi Zhang 6 7 11 12 , Guang-Hui Liu 1 4 5 6 7 , Fuchou Tang 2 8 9 , Jing Qu 3 6 7

  • 1 State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. 2Beijing Advanced Innovation Center for Genomics, Biomedical Pioneering Innovation Center, College of Life Sciences, Peking University, Beijing 100871, China. 3State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. 4National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. 5Beijing Institute for Brain Disorders, Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China. 6University of Chinese Academy of Sciences, Beijing 100049, China. 7Institute for Stem Cell and Regeneration, CAS, Beijing 100101, China. 8Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China. 9Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China. 10Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California, United States of America. 11CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China. 12 China National Center for Bioinformation, Beijing 100101, China. 13The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing 100730, 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 drives 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 β-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 β-cell-specific upregulation of HSP90B1, an endoplasmic reticulum (ER)-located chaperone, impeded high glucose-induced insulin secretion. Our work decodes aging-associated transcriptomic changes that underlie pancreatic islet functional decay at the single-cell resolution and indicates that targeting UPR components may prevent loss of proteostasis, suggesting an avenue to delaying β-cell aging and preventing aging-related diabetes.

view this paper in scRNA-Seq database