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Delineating mouse β-cell identity during lifetime and in diabetes with a single cell atlas.
Nat. Metab. 5, 1615-1637 (2023)
Although multiple pancreatic islet single-cell RNA-sequencing (scRNA-seq) datasets have been generated, a consensus on pancreatic cell states in development, homeostasis and diabetes as well as the value of preclinical animal models is missing. Here, we present an scRNA-seq cross-condition mouse islet atlas (MIA), a curated resource for interactive exploration and computational querying. We integrate over 300,000 cells from nine scRNA-seq datasets consisting of 56 samples, varying in age, sex and diabetes models, including an autoimmune type 1 diabetes model (NOD), a glucotoxicity/lipotoxicity type 2 diabetes model (db/db) and a chemical streptozotocin β-cell ablation model. The β-cell landscape of MIA reveals new cell states during disease progression and cross-publication differences between previously suggested marker genes. We show that β-cells in the streptozotocin model transcriptionally correlate with those in human type 2 diabetes and mouse db/db models, but are less similar to human type 1 diabetes and mouse NOD β-cells. We also report pathways that are shared between β-cells in immature, aged and diabetes models. MIA enables a comprehensive analysis of β-cell responses to different stressors, providing a roadmap for the understanding of β-cell plasticity, compensation and demise.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Unfolded Protein Response; Gene-expression; Pancreatic-islets; Delta Cells; Reveals; Dedifferentiation; Mechanisms; Transcriptomes; Heterogeneity; Dysfunction
ISSN (print) / ISBN
2522-5812
e-ISSN
2522-5812
Journal
Nature metabolism
Quellenangaben
Volume: 5,
Issue: 9,
Pages: 1615-1637
Publisher
Springer
Publishing Place
London
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Computational Biology (ICB)
Institute of Diabetes and Regeneration Research (IDR)
Institute of Diabetes and Regeneration Research (IDR)
Grants
Helmholtz Zentrum Munchen Deutsches Forschungszentrum fur Gesundheit und Umwelt (GmbH)