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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
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.
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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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