التفاصيل البيبلوغرافية
| العنوان: |
An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells. |
| المؤلفون: |
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. |
| المصدر: |
Nature Communications; 5/22/2020, Vol. 11 Issue 1, p1-17, 17p |
| مصطلحات موضوعية: |
PANCREATIC beta cells, INTERFERON receptors, ANTIGEN presenting cells, TYPE 1 diabetes, TYPE I interferons, POST-translational modification, PROTEIN expression |
| مستخلص: |
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. The cytokine IFNα is expressed in the islets of individuals with type 1 diabetes and contributes to local inflammation and destruction of beta cells. Here, the authors provide a global multiomics view of IFNα-induced changes in human beta cells at the level of chromatin, mRNA and protein expression. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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