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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 (IFN\u03b3) 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.<\/jats:p>","DOI":"10.1038\/s42003-025-08918-8","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T15:25:02Z","timestamp":1760714702000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Decoding adult murine pancreatic islet cell diversity through cell type-resolved proteomics and phosphoproteomics"],"prefix":"10.1038","volume":"8","author":[{"given":"Marvin","family":"Thielert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Villalba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenth","family":"Brennsteiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2079-4402","authenticated-orcid":false,"given":"Maria","family":"Wahle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantin","family":"Ammar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2733-7899","authenticated-orcid":false,"given":"Andreas-David","family":"Brunner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Fouque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chlo\u00e9","family":"Louren\u00e7o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaya","family":"Oshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1089-2837","authenticated-orcid":false,"given":"Latif","family":"Rachdi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8259-3329","authenticated-orcid":false,"given":"Willem","family":"Staels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1292-4799","authenticated-orcid":false,"given":"Matthias","family":"Mann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7619-337X","authenticated-orcid":false,"given":"Rapha\u00ebl","family":"Scharfmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"8918_CR1","doi-asserted-by":"publisher","first-page":"1962","DOI":"10.1007\/s00125-020-05235-z","volume":"63","author":"SM Marshall","year":"2020","unstructured":"Marshall, S. 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