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

被引:1131
作者
Segerstolpe, Asa [1 ,2 ]
Palasantza, Athanasia [1 ]
Eliasson, Pernilla [3 ]
Andersson, Eva-Marie [3 ]
Andreasson, Anne-Christine [3 ]
Sun, Xiaoyan [4 ,5 ]
Picelli, Simone [6 ,10 ]
Sabirsh, Alan [3 ]
Clausen, Maryam [7 ]
Bjursell, Magnus K. [8 ]
Smith, David M. [9 ]
Kasper, Maria [4 ,5 ]
Ammala, Carina [3 ]
Sandberg, Rickard [1 ,2 ,6 ]
机构
[1] Karolinska Inst, Dept Cell & Mol Biol CMB, S-17177 Stockholm, Sweden
[2] Karolinska Inst, Integrated Cardio Metab Ctr ICMC, S-14157 Huddinge, Sweden
[3] AstraZeneca, Innovat Med & Early Dev Biotech Unit IMed, Cardiovasc & Metab Dis CVMD, S-43183 Molndal, Sweden
[4] Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden
[5] Karolinska Inst, Ctr Innovat Med, Novum, S-14183 Huddinge, Sweden
[6] Ludwig Inst Canc Res, S-17177 Stockholm, Sweden
[7] AstraZeneca, Discovery Sci Innovat Med & Early Dev Biotech Uni, S-43183 Molndal, Sweden
[8] AstraZeneca, RDI, S-43183 Molndal, Sweden
[9] AstraZeneca, Discovery Sci Innovat Med & Early Dev Biotech Uni, Cambridge Sci Pk,Milton Rd, Cambridge CB4 0WG, England
[10] Sci Life Lab, S-17165 Stockholm, Sweden
基金
瑞典研究理事会; 欧洲研究理事会;
关键词
BETA-CELLS; RNA-SEQ; INSULIN-RESISTANCE; ALPHA-CELLS; OBESITY; LEPTIN; ACTIVATION; GHRELIN; CONTRIBUTES; INVOLVEMENT;
D O I
10.1016/j.cmet.2016.08.020
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
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 delta, gamma, epsilon, and stellate cells, and revealed subpopulations of alpha, beta, and acinar cells. Intriguingly, delta 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.
引用
收藏
页码:593 / 607
页数:15
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