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| Pàgina inicial > Articles > Articles publicats > An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells |
(ULB Center for Diabetes Research. Medical Faculty. Université Libre de Bruxelles) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Biological Sciences Division. Pacific Northwest National Laboratory) (ULB Center for Diabetes Research. Medical Faculty. Université Libre de Bruxelles) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Department of Clinical and Experimental Medicine. Islet Cell Laboratory. University of Pisa) (Institute of Biomedical & Clinical Science. University of Exeter Medical School) (Institute of Biomedical & Clinical Science. University of Exeter Medical School) (Biological Sciences Division. Pacific Northwest National Laboratory) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Indiana Biosciences Research Institute)| Data: | 2020 |
| Resum: | 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. |
| Ajuts: | Agencia Estatal de Investigación SAF2017-86242-R European Commission 115797 European Commission 667191 Ministerio de Economía y Competitividad RYC-2013-12864 |
| Nota: | Altres ajuts: This work was supported by grants from Marató TV3 (201624.10 to L.P.). M.R. is supported by an FI Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) PhD fellowship. |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | Alternative Splicing ; Cells, Cultured ; Chromatin ; Data Mining ; Diabetes Mellitus, Type 1 ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; Insulin-Secreting Cells ; Interferon-alpha ; Protein Interaction Maps ; Proteomics ; Transcription Factors ; Transcription Initiation Site |
| Publicat a: | Nature communications, Vol. 11 Núm. 1 (january 2020) , p. 2584, ISSN 2041-1723 |
