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

• DOI: 10.1038/s41467-020-16327-0
• Publication Date: 2020-05-22T10:03:39Z
• Authors: Maikel L. Colli; Mireia Ramos-Rodr...; Ernesto S. Nakayasu; Maria I. Alvelos; Miguel Lopes; Jessica L. E. Hill; Jean-Valery Turat...; Alexandra Coomans...; Mark A. Russell; Helena Raurell-Vila; Angela Castela; Jonàs Juan-Mateu; Bobbie-Jo M. Webb...; Lars Krogvold; Knut Dahl-Jorgensen; Lorella Marselli; Piero Marchetti; Sarah J. Richardson; Noel G. Morgan; Thomas O. Metz; Lorenzo Pasquali; Décio L. Eizirik
• Keywords: BETA (programming language); IRF1

Abstract Interferon-α (IFNα), a type I interferon, is expressed in the islets of 1 diabetic individuals, and its expression signaling are regulated by T1D genetic risk variants viral infections associated with T1D. We presently characterize human beta cell responses to IFNα combining ATAC-seq, RNA-seq proteomics assays. The initial response characterized chromatin remodeling, followed changes transcriptional translational regulation. induces alternative splicing (AS) first exon usage, increasing diversity transcripts cells. This, combined observed on protein modification/degradation, ER stress MHC class I, may expand antigens presented cells immune system. Beta also up-regulate checkpoint proteins PDL1 HLA-E that exert protective role against autoimmune assault. Data mining present multi-omics analysis identifies two compound classes antagonize effects