Single-cell multi-omics analysis of human pancreatic islets reveals novel cellular states in type 1 diabetes

Type 1 diabetes (T1D) is an autoimmune disease in which immune cells destroy insulin-producing beta cells. The aetiology of this complex disease is dependent on the interplay of multiple heterogeneous cell types in the pancreatic environment. Here, we provide a single-cell atlas of pancreatic islets of 24 T1D, autoantibody-positive and nondiabetic organ donors across multiple quantitative modalities including similar to 80,000 cells using single-cell transcriptomics, similar to 7,000,000 cells using cytometry by time of flight and similar to 1,000,000 cells using in situ imaging mass cytometry. We develop an advanced integrative analytical strategy to assess pancreatic islets and identify canonical cell types. We show that a subset of exocrine ductal cells acquires a signature of tolerogenic dendritic cells in an apparent attempt at immune suppression in T1D donors. Our multimodal analyses delineate cell types and processes that may contribute to T1D immunopathogenesis and provide an integrative procedure for exploration and discovery of human pancreatic function.

Automated summary

This study provides a single-cell atlas of pancreatic islets in patients with type 1 diabetes, revealing potential immune cell activities and cell types. It offers important insights for studying the etiology of diabetes and developing new treatment approaches.