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<p>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.</p>

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Decoding adult murine pancreatic islet cell diversity through cell type-resolved proteomics and phosphoproteomics

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月17日

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  • Marvin Thielert,
  • Adrian Villalba,
  • Vincenth Brennsteiner,
  • Maria Wahle,
  • Constantin Ammar,
  • Andreas-David Brunner,
  • Alexis Fouque,
  • Chloé Lourenço,
  • Masaya Oshima,
  • Latif Rachdi,
  • Willem Staels,
  • Matthias Mann,
  • Raphaël Scharfmann

摘要

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.