Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes.
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.
Department of Cell and Molecular Biology (CMB), Karolinska Institutet, 171 77 Stockholm, Sweden; Integrated Cardio Metabolic Center (ICMC), Karolinska Institutet, 141 57 Huddinge, Sweden.
Åsa
Å
Segerstolpe
Department of Cell and Molecular Biology (CMB), Karolinska Institutet, 171 77 Stockholm, Sweden.
Athanasia
A
Palasantza
Cardiovascular and Metabolic Diseases (CVMD), Innovative Medicines and Early Development Biotech Unit (iMed), AstraZeneca, 431 83 Mölndal, Sweden.
Pernilla
P
Eliasson
Cardiovascular and Metabolic Diseases (CVMD), Innovative Medicines and Early Development Biotech Unit (iMed), AstraZeneca, 431 83 Mölndal, Sweden.
Eva-Marie
EM
Andersson
Cardiovascular and Metabolic Diseases (CVMD), Innovative Medicines and Early Development Biotech Unit (iMed), AstraZeneca, 431 83 Mölndal, Sweden.
Anne-Christine
AC
Andréasson
Department of Biosciences and Nutrition and Center for Innovative Medicine, Novum, Karolinska Institutet, 141 83 Huddinge, Sweden.
Xiaoyan
X
Sun
Ludwig Institute for Cancer Research, 171 77 Stockholm, Sweden.
Simone
S
Picelli
Cardiovascular and Metabolic Diseases (CVMD), Innovative Medicines and Early Development Biotech Unit (iMed), AstraZeneca, 431 83 Mölndal, Sweden.
Alan
A
Sabirsh
Discovery Sciences, Innovative Medicines and Early Development Biotech Unit (iMed), AstraZeneca, 431 83 Mölndal, Sweden.
Maryam
M
Clausen
R&D Information (RDI), AstraZeneca, 431 83 Mölndal, Sweden.
Magnus K
MK
Bjursell
Discovery Sciences, Innovative Medicines and Early Development Biotech Unit (iMed), AstraZeneca, Cambridge Science Park, Milton Road, Cambridge CB4 0WG, UK.
David M
DM
Smith
Department of Biosciences and Nutrition and Center for Innovative Medicine, Novum, Karolinska Institutet, 141 83 Huddinge, Sweden.
Maria
M
Kasper
Cardiovascular and Metabolic Diseases (CVMD), Innovative Medicines and Early Development Biotech Unit (iMed), AstraZeneca, 431 83 Mölndal, Sweden.
Carina
C
Ämmälä
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.
Rickard
R
Sandberg
D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology*; D020869:Gene Expression Profiling / Q000379:methods*; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000235:genetics; D015203:Reproducibility of Results; D059010:Single-Cell Analysis / Q000379:methods*; D014019:Tissue Donors; D014157:Transcription Factors / Q000378:metabolism
C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D014157:Transcription Factors
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