Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes
Open accessAbstract
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.
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Chronic hyperglycemia is associated with marked changes in expression of metabolic genes in mouse β-cells, and similar changes are observed in islets from individuals with T2DM.
“Chronic hyperglycemia is also associated with marked changes in expression of metabolic genes in mouse β-cells (97) and similar changes are observed in islets from individuals with T2DM (409, 430, 606).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [606]
The effect of KCNJ15 on T2DM risk is probably mediated via other cell types.
“As KCNJ15 is expressed at low, albeit detectable, levels in human β-cells (Appendix Figure 7), and there is no evidence its expression is increased in diabetic β-cells (606), its effect on T2DM risk is probably mediated via other cell types.”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [606]
The citation is attached to the statement that there is no evidence of increased KCNJ15 expression in diabetic β-cells; the proposed effect through other cell types is the citing authors’ inference. The Results section on gene-expression alterations in T2D discusses other β-cell genes but does not address KCNJ15. Searches for KCNJ15 and its expression in diabetic β-cells found no relevant passage in our copy; page numbers were unavailable. (LLM, conf=0.72)
Experimental — accuracy not yet measuredCell type and state compositions differ between experimental conditions.
“As cell type and state compositions differ between experimental conditions (Segerstolpe et al, 2016; Tanay & Regev, 2017)”
From Current best practices in single-cell RNA-seq analysis: a tutorial (2019) · cites this paper as Segerstolpe et al, 2016
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- Authors
- Segerstolpe, Å., Palasantza, A., Eliasson, P., Andersson, E.-M., Andréasson, A.-C., Sun, X., Picelli, S., Sabirsh, A., Clausen, M., Bjursell, M. K., Smith, D. M., Kasper, M., Ämmälä, C., & Sandberg, R.
- Affiliations
- Karolinska Institutet (SE)
- AstraZeneca (Sweden) (SE)
- Ludwig Cancer Research (SE)
- AstraZeneca (United Kingdom) (GB)
- Corresponding author
- Sandberg, Rickard
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 24
- Issue
- 4
- Pages
- 593-607
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC5069352
- OpenAlex
- W2523369352
- Cited by
- 1,550
- References
- 53
- Citations by year
- 2026: 100 · 2025: 134 · 2024: 177 · 2023: 201 · 2022: 179 · 2021: 239 · 2020: 189 · 2019: 140 · 2018: 110 · 2017: 69 · 2016: 7 · 2014: 1
- FWCI
- 120.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by)
- Funders
- Science for Life Laboratory
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- pancreatic islets, type 2 diabetes, single-cell transcriptomics, islet cell types, endocrine cells, delta cells, stellate cells, alpha cells, pancreatic beta cells, cell type-specific gene expression, obesity, body mass index, paracrine signaling
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Diabetes Mellitus, Type 2, Humans, Islets of Langerhans, Male, Obesity, Tissue Donors, Transcription Factors, Reproducibility of Results, Gene Expression Profiling, Single-Cell Analysis
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