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Single-Cell Transcriptomics Links Loss of Human Pancreatic β-Cell Identity to ER Stress
The maintenance of pancreatic islet architecture is crucial for proper β-cell function. We previously reported that disruption of human islet integrity could result in altered β-cell identity. Here we combine β-cell lineage tracing and single-cell transcriptomics to investigate the mechanisms underl...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700697/ https://www.ncbi.nlm.nih.gov/pubmed/34944092 http://dx.doi.org/10.3390/cells10123585 |
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author | Groen, Nathalie Leenders, Floris Mahfouz, Ahmed Munoz-Garcia, Amadeo Muraro, Mauro J. de Graaf, Natascha Rabelink, Ton. J. Hoeben, Rob van Oudenaarden, Alexander Zaldumbide, Arnaud Reinders, Marcel J. T. de Koning, Eelco J. P. Carlotti, Françoise |
author_facet | Groen, Nathalie Leenders, Floris Mahfouz, Ahmed Munoz-Garcia, Amadeo Muraro, Mauro J. de Graaf, Natascha Rabelink, Ton. J. Hoeben, Rob van Oudenaarden, Alexander Zaldumbide, Arnaud Reinders, Marcel J. T. de Koning, Eelco J. P. Carlotti, Françoise |
author_sort | Groen, Nathalie |
collection | PubMed |
description | The maintenance of pancreatic islet architecture is crucial for proper β-cell function. We previously reported that disruption of human islet integrity could result in altered β-cell identity. Here we combine β-cell lineage tracing and single-cell transcriptomics to investigate the mechanisms underlying this process in primary human islet cells. Using drug-induced ER stress and cytoskeleton modification models, we demonstrate that altering the islet structure triggers an unfolding protein response that causes the downregulation of β-cell maturity genes. Collectively, our findings illustrate the close relationship between endoplasmic reticulum homeostasis and β-cell phenotype, and strengthen the concept of altered β-cell identity as a mechanism underlying the loss of functional β-cell mass. |
format | Online Article Text |
id | pubmed-8700697 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87006972021-12-24 Single-Cell Transcriptomics Links Loss of Human Pancreatic β-Cell Identity to ER Stress Groen, Nathalie Leenders, Floris Mahfouz, Ahmed Munoz-Garcia, Amadeo Muraro, Mauro J. de Graaf, Natascha Rabelink, Ton. J. Hoeben, Rob van Oudenaarden, Alexander Zaldumbide, Arnaud Reinders, Marcel J. T. de Koning, Eelco J. P. Carlotti, Françoise Cells Article The maintenance of pancreatic islet architecture is crucial for proper β-cell function. We previously reported that disruption of human islet integrity could result in altered β-cell identity. Here we combine β-cell lineage tracing and single-cell transcriptomics to investigate the mechanisms underlying this process in primary human islet cells. Using drug-induced ER stress and cytoskeleton modification models, we demonstrate that altering the islet structure triggers an unfolding protein response that causes the downregulation of β-cell maturity genes. Collectively, our findings illustrate the close relationship between endoplasmic reticulum homeostasis and β-cell phenotype, and strengthen the concept of altered β-cell identity as a mechanism underlying the loss of functional β-cell mass. MDPI 2021-12-19 /pmc/articles/PMC8700697/ /pubmed/34944092 http://dx.doi.org/10.3390/cells10123585 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Groen, Nathalie Leenders, Floris Mahfouz, Ahmed Munoz-Garcia, Amadeo Muraro, Mauro J. de Graaf, Natascha Rabelink, Ton. J. Hoeben, Rob van Oudenaarden, Alexander Zaldumbide, Arnaud Reinders, Marcel J. T. de Koning, Eelco J. P. Carlotti, Françoise Single-Cell Transcriptomics Links Loss of Human Pancreatic β-Cell Identity to ER Stress |
title | Single-Cell Transcriptomics Links Loss of Human Pancreatic β-Cell Identity to ER Stress |
title_full | Single-Cell Transcriptomics Links Loss of Human Pancreatic β-Cell Identity to ER Stress |
title_fullStr | Single-Cell Transcriptomics Links Loss of Human Pancreatic β-Cell Identity to ER Stress |
title_full_unstemmed | Single-Cell Transcriptomics Links Loss of Human Pancreatic β-Cell Identity to ER Stress |
title_short | Single-Cell Transcriptomics Links Loss of Human Pancreatic β-Cell Identity to ER Stress |
title_sort | single-cell transcriptomics links loss of human pancreatic β-cell identity to er stress |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700697/ https://www.ncbi.nlm.nih.gov/pubmed/34944092 http://dx.doi.org/10.3390/cells10123585 |
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