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A single-cell transcriptomic atlas of primate pancreatic islet aging
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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288398/ https://www.ncbi.nlm.nih.gov/pubmed/34691567 http://dx.doi.org/10.1093/nsr/nwaa127 |
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author | Li, Jingyi Zheng, Yuxuan Yan, Pengze Song, Moshi Wang, Si Sun, Liang Liu, Zunpeng Ma, Shuai Izpisua Belmonte, Juan Carlos Chan, Piu Zhou, Qi Zhang, Weiqi Liu, Guang-Hui Tang, Fuchou Qu, Jing |
author_facet | Li, Jingyi Zheng, Yuxuan Yan, Pengze Song, Moshi Wang, Si Sun, Liang Liu, Zunpeng Ma, Shuai Izpisua Belmonte, Juan Carlos Chan, Piu Zhou, Qi Zhang, Weiqi Liu, Guang-Hui Tang, Fuchou Qu, Jing |
author_sort | Li, Jingyi |
collection | PubMed |
description | 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 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-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 β-cell aging and preventing aging-related diabetes. |
format | Online Article Text |
id | pubmed-8288398 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-82883982021-10-21 A single-cell transcriptomic atlas of primate pancreatic islet aging Li, Jingyi Zheng, Yuxuan Yan, Pengze Song, Moshi Wang, Si Sun, Liang Liu, Zunpeng Ma, Shuai Izpisua Belmonte, Juan Carlos Chan, Piu Zhou, Qi Zhang, Weiqi Liu, Guang-Hui Tang, Fuchou Qu, Jing Natl Sci Rev Molecular Biology & Genetics 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 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-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 β-cell aging and preventing aging-related diabetes. Oxford University Press 2020-06-10 /pmc/articles/PMC8288398/ /pubmed/34691567 http://dx.doi.org/10.1093/nsr/nwaa127 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Molecular Biology & Genetics Li, Jingyi Zheng, Yuxuan Yan, Pengze Song, Moshi Wang, Si Sun, Liang Liu, Zunpeng Ma, Shuai Izpisua Belmonte, Juan Carlos Chan, Piu Zhou, Qi Zhang, Weiqi Liu, Guang-Hui Tang, Fuchou Qu, Jing A single-cell transcriptomic atlas of primate pancreatic islet aging |
title | A single-cell transcriptomic atlas of primate pancreatic islet aging |
title_full | A single-cell transcriptomic atlas of primate pancreatic islet aging |
title_fullStr | A single-cell transcriptomic atlas of primate pancreatic islet aging |
title_full_unstemmed | A single-cell transcriptomic atlas of primate pancreatic islet aging |
title_short | A single-cell transcriptomic atlas of primate pancreatic islet aging |
title_sort | single-cell transcriptomic atlas of primate pancreatic islet aging |
topic | Molecular Biology & Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288398/ https://www.ncbi.nlm.nih.gov/pubmed/34691567 http://dx.doi.org/10.1093/nsr/nwaa127 |
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