Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes
- PMID: 27667667
- PMCID: PMC5069352
- DOI: 10.1016/j.cmet.2016.08.020
Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes
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.
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Figures
![Image 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/5069352/bin/fx1.gif)
![Figure 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/5069352/bin/gr1.gif)
![Figure 2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/5069352/bin/gr2.gif)
![Figure 3](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/5069352/bin/gr3.gif)
![Figure 4](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/5069352/bin/gr4.gif)
![Figure 5](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/5069352/bin/gr5.gif)
![Figure 6](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/5069352/bin/gr6.gif)
![Figure 7](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/5069352/bin/gr7.gif)
Comment in
-
Single-Cell Sequencing of Human Pancreatic Islets-New Kids on the Block.Cell Metab. 2016 Oct 11;24(4):523-524. doi: 10.1016/j.cmet.2016.09.012. Cell Metab. 2016. PMID: 27732832
-
Diabetes: Transcriptomes reveal specific islet cell signatures.Nat Rev Endocrinol. 2016 Dec;12(12):686. doi: 10.1038/nrendo.2016.173. Epub 2016 Oct 14. Nat Rev Endocrinol. 2016. PMID: 27739516 No abstract available.
Similar articles
-
Single-cell transcriptomics of human islet ontogeny defines the molecular basis of β-cell dedifferentiation in T2D.Mol Metab. 2020 Dec;42:101057. doi: 10.1016/j.molmet.2020.101057. Epub 2020 Jul 30. Mol Metab. 2020. PMID: 32739450 Free PMC article.
-
Single-cell ATAC-Seq in human pancreatic islets and deep learning upscaling of rare cells reveals cell-specific type 2 diabetes regulatory signatures.Mol Metab. 2020 Feb;32:109-121. doi: 10.1016/j.molmet.2019.12.006. Epub 2019 Dec 20. Mol Metab. 2020. PMID: 32029221 Free PMC article.
-
Interrogating islets in health and disease with single-cell technologies.Mol Metab. 2017 May 5;6(9):991-1001. doi: 10.1016/j.molmet.2017.04.012. eCollection 2017 Sep. Mol Metab. 2017. PMID: 28951823 Free PMC article. Review.
-
Genomics of Islet (Dys)function and Type 2 Diabetes.Trends Genet. 2017 Apr;33(4):244-255. doi: 10.1016/j.tig.2017.01.010. Epub 2017 Feb 27. Trends Genet. 2017. PMID: 28245910 Free PMC article. Review.
-
Single-cell transcriptomes identify human islet cell signatures and reveal cell-type-specific expression changes in type 2 diabetes.Genome Res. 2017 Feb;27(2):208-222. doi: 10.1101/gr.212720.116. Epub 2016 Nov 18. Genome Res. 2017. PMID: 27864352 Free PMC article.
Cited by
-
A single-cell strategy for the identification of intronic variants related to mis-splicing in pancreatic cancer.NAR Genom Bioinform. 2024 May 25;6(2):lqae057. doi: 10.1093/nargab/lqae057. eCollection 2024 Jun. NAR Genom Bioinform. 2024. PMID: 38800828 Free PMC article.
-
Improving replicability in single-cell RNA-Seq cell type discovery with Dune.BMC Bioinformatics. 2024 May 24;25(1):198. doi: 10.1186/s12859-024-05814-6. BMC Bioinformatics. 2024. PMID: 38789920 Free PMC article.
-
Pancreatic β-Cell Identity Change through the Lens of Single-Cell Omics Research.Int J Mol Sci. 2024 Apr 26;25(9):4720. doi: 10.3390/ijms25094720. Int J Mol Sci. 2024. PMID: 38731945 Free PMC article. Review.
-
Acinar to β-like cell conversion through inhibition of focal adhesion kinase.Nat Commun. 2024 May 3;15(1):3740. doi: 10.1038/s41467-024-47972-4. Nat Commun. 2024. PMID: 38702347 Free PMC article.
-
DISSECT: deep semi-supervised consistency regularization for accurate cell type fraction and gene expression estimation.Genome Biol. 2024 Apr 30;25(1):112. doi: 10.1186/s13059-024-03251-5. Genome Biol. 2024. PMID: 38689377 Free PMC article.
References
-
- Braks J.A., Martens G.J. 7B2 is a neuroendocrine chaperone that transiently interacts with prohormone convertase PC2 in the secretory pathway. Cell. 1994;78:263–273. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical