Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes

Cell Metab. 2016 Oct 11;24(4):593-607. doi: 10.1016/j.cmet.2016.08.020. Epub 2016 Sep 22.

Abstract

Hormone-secreting cells within pancreatic islets of Langerhans play important roles in metabolic homeostasis and disease. However, their transcriptional characterization is still incomplete. Here, we sequenced the transcriptomes of thousands of human islet cells from healthy and type 2 diabetic donors. We could define specific genetic programs for each individual endocrine and exocrine cell type, even for rare δ, γ, ε, and stellate cells, and revealed subpopulations of α, β, and acinar cells. Intriguingly, δ cells expressed several important receptors, indicating an unrecognized importance of these cells in integrating paracrine and systemic metabolic signals. Genes previously associated with obesity or diabetes were found to correlate with BMI. Finally, comparing healthy and T2D transcriptomes in a cell-type resolved manner uncovered candidates for future functional studies. Altogether, our analyses demonstrate the utility of the generated single-cell gene expression resource.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / pathology*
  • Gene Expression Profiling / methods*
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Humans
  • Islets of Langerhans / metabolism*
  • Male
  • Obesity / genetics
  • Reproducibility of Results
  • Single-Cell Analysis / methods*
  • Tissue Donors
  • Transcription Factors / metabolism

Substances

  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Transcription Factors