An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells.

Autor:	Colli ML; ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, Brussels, 1070, Belgium. mcolli@ulb.ac.be., Ramos-Rodríguez M; Endocrine Regulatory Genomics, Department of Experimental & Health Sciences, University Pompeu Fabra, 08003, Barcelona, Spain.; Endocrine Regulatory Genomics Laboratory, Germans Trias i Pujol University Hospital and Research Institute, Badalona, Spain., Nakayasu ES; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99352, USA., Alvelos MI; ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, Brussels, 1070, Belgium., Lopes M; ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, Brussels, 1070, Belgium., Hill JLE; Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, EX2 5DW, UK., Turatsinze JV; ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, Brussels, 1070, Belgium., Coomans de Brachène A; ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, Brussels, 1070, Belgium., Russell MA; Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, EX2 5DW, UK., Raurell-Vila H; Endocrine Regulatory Genomics, Department of Experimental & Health Sciences, University Pompeu Fabra, 08003, Barcelona, Spain.; Endocrine Regulatory Genomics Laboratory, Germans Trias i Pujol University Hospital and Research Institute, Badalona, Spain., Castela A; ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, Brussels, 1070, Belgium., Juan-Mateu J; ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, Brussels, 1070, Belgium., Webb-Robertson BM; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99352, USA., Krogvold L; Division of Pediatric and Adolescent Medicine, Faculty of Medicine, Oslo University Hospital, Oslo, Norway., Dahl-Jorgensen K; Division of Pediatric and Adolescent Medicine, Faculty of Medicine, Oslo University Hospital, Oslo, Norway., Marselli L; Department of Clinical and Experimental Medicine, Islet Cell Laboratory, University of Pisa, 56126, Pisa, Italy., Marchetti P; Department of Clinical and Experimental Medicine, Islet Cell Laboratory, University of Pisa, 56126, Pisa, Italy., Richardson SJ; Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, EX2 5DW, UK., Morgan NG; Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, EX2 5DW, UK., Metz TO; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99352, USA., Pasquali L; Endocrine Regulatory Genomics, Department of Experimental & Health Sciences, University Pompeu Fabra, 08003, Barcelona, Spain.; Endocrine Regulatory Genomics Laboratory, Germans Trias i Pujol University Hospital and Research Institute, Badalona, Spain.; Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain., Eizirik DL; ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, Brussels, 1070, Belgium.; WELBIO, Université Libre de Bruxelles, Brussels, Belgium.; Indiana Biosciences Research Institute, Indianapolis, IN, USA.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2020 May 22; Vol. 11 (1), pp. 2584. Date of Electronic Publication: 2020 May 22.
DOI:	10.1038/s41467-020-16327-0
Abstrakt:	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.
Databáze:	MEDLINE
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