Introduction and Objective: Single-cell RNA sequencing (scRNA-seq) analysis of pancreatic islet tissues is powerful for studying Type 1 and Type 2 Diabetes (T1D and T2D). Despite many existing efforts, individual datasets are modest in size and fragmented across donors, labs and conditions, highlighting the need for a single-cell (SC) atlas that collates information from diverse sources. To address this, we aggregated islet scRNA-seq data from various studies and tissue distribution centers, applied rigorous quality control (QC) and computational integration to create a harmonized resource.Methods: Raw scRNA-seq data from studies utilizing cadaveric islets, generated and/or provided by the Human Pancreas Analysis Program, Integrated Islet Distribution Program, and Prodo Labs, were collected. The sequencing data were aligned, and genotype and metadata checks were conducted to verify donor information. Systematic QCs were implemented to select high-quality cells, adjust for ambient RNA, and identify doublets. Data integration was performed using the Harmony algorithm, adjusting for covariates like sex, BMI, age, study design, tissue sources and sequencing chemistry.Results: Our SC map integrates data from 132 donors (56 female, 76 male) across four phenotypes: 77 non-diabetic, 11 pre-diabetic, 11 T1D, and 33 T2D. It comprises 284 samples covering cell treatments such as SARS-CoV-2 infection and cytokine-induced inflammation. The atlas features 565,388 cells across 13 major cell populations, with high-abundance populations such as alpha and beta cells (39.9% and 28.3% cell counts, respectively), and lower-abundance ones like immune cells (0.64%).Conclusion: By integrating data from multiple sources, we have constructed a comprehensive SC map of islet tissues, available at www.PanKbase.org, to fuel hypothesis testing for diabetes pathophysiology. We are conducting analyses including differential gene expression and cell abundance to gain deeper insights into T1D and T2D mechanisms.
H.T.H. Vu: None. H. Sun: None. S. Sharp: None. L. Brusman: None. F. Feng: None. R. Mao: None. Y. Wang: None. S. Corban: None. Y. Huang: None. A.K. Huber: None. A. Shilin: None. D. Jang: None. J. Jurgens: None. C. Robertson: None. T. Nguyen: None. Y. Sun: None. M. Brandes: None. P. Smadbeck: None. S. Narayanaswamy: None. T.S. Bate: None. J. Flannick: None. N. Burtt: None. J. Liu: None. M.L. Stitzel: None. J. Cartailler: None. B.F. Voight: Other Relationship; Eli Lilly and Company. M. Brissova: None. A.L. Gloyn: Other Relationship; Genentech, Inc, Roche Pharmaceuticals. K.J. Gaulton: Stock/Shareholder; Neurocrine biosciences. Other Relationship; Altos labs, Pfizer Inc. Consultant; Genentech, Inc. S.C. Parker: Research Support; Pfizer Inc.
National Institute of Diabetes and Digestive and Kidney Diseases (U24DK138515, U24DK138512)
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