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An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells
Interferon-α (IFNα), a type I interferon, is expressed in the islets of type 1 diabetic individuals, and its expression and signaling are regulated by T1D genetic risk variants and viral infections associated with T1D. We presently characterize human beta cell responses to IFNα by combining ATAC-seq...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244579/ https://www.ncbi.nlm.nih.gov/pubmed/32444635 http://dx.doi.org/10.1038/s41467-020-16327-0 |
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author | Colli, Maikel L. Ramos-Rodríguez, Mireia Nakayasu, Ernesto S. Alvelos, Maria I. Lopes, Miguel Hill, Jessica L. E. Turatsinze, Jean-Valery Coomans de Brachène, Alexandra Russell, Mark A. Raurell-Vila, Helena Castela, Angela Juan-Mateu, Jonàs Webb-Robertson, Bobbie-Jo M. Krogvold, Lars Dahl-Jorgensen, Knut Marselli, Lorella Marchetti, Piero Richardson, Sarah J. Morgan, Noel G. Metz, Thomas O. Pasquali, Lorenzo Eizirik, Décio L. |
author_facet | Colli, Maikel L. Ramos-Rodríguez, Mireia Nakayasu, Ernesto S. Alvelos, Maria I. Lopes, Miguel Hill, Jessica L. E. Turatsinze, Jean-Valery Coomans de Brachène, Alexandra Russell, Mark A. Raurell-Vila, Helena Castela, Angela Juan-Mateu, Jonàs Webb-Robertson, Bobbie-Jo M. Krogvold, Lars Dahl-Jorgensen, Knut Marselli, Lorella Marchetti, Piero Richardson, Sarah J. Morgan, Noel G. Metz, Thomas O. Pasquali, Lorenzo Eizirik, Décio L. |
author_sort | Colli, Maikel L. |
collection | PubMed |
description | Interferon-α (IFNα), a type I interferon, is expressed in the islets of type 1 diabetic individuals, and its expression and signaling are regulated by T1D genetic risk variants and viral infections associated with T1D. We presently characterize human beta cell responses to IFNα by combining ATAC-seq, RNA-seq and proteomics assays. The initial response to IFNα is characterized by chromatin remodeling, followed by changes in transcriptional and translational regulation. IFNα induces changes in alternative splicing (AS) and first exon usage, increasing the diversity of transcripts expressed by the beta cells. This, combined with changes observed on protein modification/degradation, ER stress and MHC class I, may expand antigens presented by beta cells to the immune system. Beta cells also up-regulate the checkpoint proteins PDL1 and HLA-E that may exert a protective role against the autoimmune assault. Data mining of the present multi-omics analysis identifies two compound classes that antagonize IFNα effects on human beta cells. |
format | Online Article Text |
id | pubmed-7244579 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-72445792020-06-03 An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells Colli, Maikel L. Ramos-Rodríguez, Mireia Nakayasu, Ernesto S. Alvelos, Maria I. Lopes, Miguel Hill, Jessica L. E. Turatsinze, Jean-Valery Coomans de Brachène, Alexandra Russell, Mark A. Raurell-Vila, Helena Castela, Angela Juan-Mateu, Jonàs Webb-Robertson, Bobbie-Jo M. Krogvold, Lars Dahl-Jorgensen, Knut Marselli, Lorella Marchetti, Piero Richardson, Sarah J. Morgan, Noel G. Metz, Thomas O. Pasquali, Lorenzo Eizirik, Décio L. Nat Commun Article Interferon-α (IFNα), a type I interferon, is expressed in the islets of type 1 diabetic individuals, and its expression and signaling are regulated by T1D genetic risk variants and viral infections associated with T1D. We presently characterize human beta cell responses to IFNα by combining ATAC-seq, RNA-seq and proteomics assays. The initial response to IFNα is characterized by chromatin remodeling, followed by changes in transcriptional and translational regulation. IFNα induces changes in alternative splicing (AS) and first exon usage, increasing the diversity of transcripts expressed by the beta cells. This, combined with changes observed on protein modification/degradation, ER stress and MHC class I, may expand antigens presented by beta cells to the immune system. Beta cells also up-regulate the checkpoint proteins PDL1 and HLA-E that may exert a protective role against the autoimmune assault. Data mining of the present multi-omics analysis identifies two compound classes that antagonize IFNα effects on human beta cells. Nature Publishing Group UK 2020-05-22 /pmc/articles/PMC7244579/ /pubmed/32444635 http://dx.doi.org/10.1038/s41467-020-16327-0 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Colli, Maikel L. Ramos-Rodríguez, Mireia Nakayasu, Ernesto S. Alvelos, Maria I. Lopes, Miguel Hill, Jessica L. E. Turatsinze, Jean-Valery Coomans de Brachène, Alexandra Russell, Mark A. Raurell-Vila, Helena Castela, Angela Juan-Mateu, Jonàs Webb-Robertson, Bobbie-Jo M. Krogvold, Lars Dahl-Jorgensen, Knut Marselli, Lorella Marchetti, Piero Richardson, Sarah J. Morgan, Noel G. Metz, Thomas O. Pasquali, Lorenzo Eizirik, Décio L. An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells |
title | An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells |
title_full | An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells |
title_fullStr | An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells |
title_full_unstemmed | An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells |
title_short | An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells |
title_sort | integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244579/ https://www.ncbi.nlm.nih.gov/pubmed/32444635 http://dx.doi.org/10.1038/s41467-020-16327-0 |
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