Decoding adult murine pancreatic islet cell diversity through cell type-resolved proteomics and phosphoproteomics
Islets of Langerhans are micro-organs scattered throughout the pancreas. They are composed of insulin-producing beta cells, glucagon-producing alpha cells, and somatostatin-producing delta cells. While their transcriptome has been extensively analyzed, protein-level information remains limited due to cell scarcity and purification challenges. Here, we combine cell sorting with highly sensitive mass spectrometry to create the first in-depth proteomic resource of pancreatic islet cells. We achieved a depth exceeding 6000 proteins per endocrine cell population, discovering new cell type-enriched ones. Deep proteomics profiling demonstrated that all three endocrine cell types were inflamed upon interferon gamma (IFNγ) treatment, a mediator of autoimmune damage in type 1 diabetes. Resolving the phosphoproteomic landscape of alpha, beta and delta cells with more than 7000 unique phosphosites per cell type provided insights into cell-specific signaling. This omics dataset offers a valuable resource for understanding pancreatic islet biology in health and disease.
Authors
- Masaya Oshima (ORCID: https://orcid.org/0000-0002-9774-0931)
- Raphaël Scharfmann (ORCID: https://orcid.org/0000-0001-7619-337X)
- Latif Rachdi (ORCID: https://orcid.org/0000-0002-1089-2837)
- Alexis Fouque
- Marvin Thielert (ORCID: https://orcid.org/0000-0003-3639-2221)
- Willem Staels (ORCID: https://orcid.org/0000-0001-8259-3329)
- Maria Wahle (ORCID: https://orcid.org/0000-0003-2079-4402)
- Constantin Ammar (ORCID: https://orcid.org/0000-0003-4310-6908)
- Andreas‐David Brunner (ORCID: https://orcid.org/0000-0002-2733-7899)
- Chloé Lourenço
- Adrian Villalba (ORCID: https://orcid.org/0000-0003-3148-5453)
- Matthias Mann (ORCID: https://orcid.org/0000-0003-1292-4799)
- Vincenth Brennsteiner (ORCID: https://orcid.org/0009-0002-4629-481X)
Institutions
- University of Copenhagen (DK)
- Centre National de la Recherche Scientifique (FR)
- Boehringer Ingelheim (Germany) (DE)
- Vrije Universiteit Brussel (BE)
- Inserm (FR)
- Université Paris Cité (FR)
- Novo Nordisk Foundation (DK)
- Valencian International University (ES)
- Universitair Ziekenhuis Brussel (BE)
- Institut Cochin (FR)
- Max Planck Institute of Biochemistry (DE)
- Instituto de Investigación Sanitaria La Fe (ES)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-10-17
- DOI
- https://doi.org/10.1038/s42003-025-08918-8
- Citations
- 1
- Primary Topic
- Pancreatic function and diabetes
- Type
- article
- Field-Weighted Citation Impact
- 2.01
Funders
- International Max Planck Research School for Environmental, Cellular and Molecular Microbiology
- European Commission
- Agence Nationale de la Recherche
- Max-Planck-Gesellschaft
- International Max Planck Research School for Advanced Methods in Process and Systems Engineering