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.