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

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

Author information

1
Department of Cell and Molecular Biology (CMB), Karolinska Institutet, 171 77 Stockholm, Sweden; Integrated Cardio Metabolic Center (ICMC), Karolinska Institutet, 141 57 Huddinge, Sweden.
2
Department of Cell and Molecular Biology (CMB), Karolinska Institutet, 171 77 Stockholm, Sweden.
3
Cardiovascular and Metabolic Diseases (CVMD), Innovative Medicines and Early Development Biotech Unit (iMed), AstraZeneca, 431 83 Mölndal, Sweden.
4
Department of Biosciences and Nutrition and Center for Innovative Medicine, Novum, Karolinska Institutet, 141 83 Huddinge, Sweden.
5
Ludwig Institute for Cancer Research, 171 77 Stockholm, Sweden.
6
Discovery Sciences, Innovative Medicines and Early Development Biotech Unit (iMed), AstraZeneca, 431 83 Mölndal, Sweden.
7
R&D Information (RDI), AstraZeneca, 431 83 Mölndal, Sweden.
8
Discovery Sciences, Innovative Medicines and Early Development Biotech Unit (iMed), AstraZeneca, Cambridge Science Park, Milton Road, Cambridge CB4 0WG, UK.
9
Department of Cell and Molecular Biology (CMB), Karolinska Institutet, 171 77 Stockholm, Sweden; Integrated Cardio Metabolic Center (ICMC), Karolinska Institutet, 141 57 Huddinge, Sweden; Ludwig Institute for Cancer Research, 171 77 Stockholm, Sweden. Electronic address: rickard.sandberg@ki.se.

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.

PMID:
27667667
PMCID:
PMC5069352
DOI:
10.1016/j.cmet.2016.08.020
[Indexed for MEDLINE]
Free PMC Article

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