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

Author

Listed:
  • Maikel L. Colli

    (Université Libre de Bruxelles)

  • Mireia Ramos-Rodríguez

    (University Pompeu Fabra
    Germans Trias i Pujol University Hospital and Research Institute)

  • Ernesto S. Nakayasu

    (Pacific Northwest National Laboratory)

  • Maria I. Alvelos

    (Université Libre de Bruxelles)

  • Miguel Lopes

    (Université Libre de Bruxelles)

  • Jessica L. E. Hill

    (University of Exeter Medical School)

  • Jean-Valery Turatsinze

    (Université Libre de Bruxelles)

  • Alexandra Coomans de Brachène

    (Université Libre de Bruxelles)

  • Mark A. Russell

    (University of Exeter Medical School)

  • Helena Raurell-Vila

    (University Pompeu Fabra
    Germans Trias i Pujol University Hospital and Research Institute)

  • Angela Castela

    (Université Libre de Bruxelles)

  • Jonàs Juan-Mateu

    (Université Libre de Bruxelles)

  • Bobbie-Jo M. Webb-Robertson

    (Pacific Northwest National Laboratory)

  • Lars Krogvold

    (Oslo University Hospital)

  • Knut Dahl-Jorgensen

    (Oslo University Hospital)

  • Lorella Marselli

    (Islet Cell Laboratory, University of Pisa)

  • Piero Marchetti

    (Islet Cell Laboratory, University of Pisa)

  • Sarah J. Richardson

    (University of Exeter Medical School)

  • Noel G. Morgan

    (University of Exeter Medical School)

  • Thomas O. Metz

    (Pacific Northwest National Laboratory)

  • Lorenzo Pasquali

    (University Pompeu Fabra
    Germans Trias i Pujol University Hospital and Research Institute
    Josep Carreras Leukaemia Research Institute (IJC))

  • Décio L. Eizirik

    (Université Libre de Bruxelles
    Université Libre de Bruxelles
    Indiana Biosciences Research Institute)

Abstract

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.

Suggested Citation

  • Maikel L. Colli & Mireia Ramos-Rodríguez & Ernesto S. Nakayasu & Maria I. Alvelos & Miguel Lopes & Jessica L. E. Hill & Jean-Valery Turatsinze & Alexandra Coomans de Brachène & Mark A. Russell & Helen, 2020. "An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16327-0
    DOI: 10.1038/s41467-020-16327-0
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    Cited by:

    1. Marlie M. Maestas & Matthew Ishahak & Punn Augsornworawat & Daniel A. Veronese-Paniagua & Kristina G. Maxwell & Leonardo Velazco-Cruz & Erica Marquez & Jiameng Sun & Mira Shunkarova & Sarah E. Gale & , 2024. "Identification of unique cell type responses in pancreatic islets to stress," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Guanlan Xu & Tiffany D. Grimes & Truman B. Grayson & Junqin Chen & Lance A. Thielen & Hubert M. Tse & Peng Li & Matt Kanke & Tai-Tu Lin & Athena A. Schepmoes & Adam C. Swensen & Vladislav A. Petyuk & , 2022. "Exploratory study reveals far reaching systemic and cellular effects of verapamil treatment in subjects with type 1 diabetes," Nature Communications, Nature, vol. 13(1), pages 1-9, December.

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