Delineating mouse β-cell identity during lifetime and in diabetes with a single cell atlas.

Autor: Hrovatin K; Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany.; TUM School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany., Bastidas-Ponce A; Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, Neuherberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany.; Medical Faculty, Technical University of Munich, Munich, Germany., Bakhti M; Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, Neuherberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany., Zappia L; Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany.; Department of Mathematics, Technical University of Munich, Garching, Germany., Büttner M; Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany.; Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany., Salinno C; Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, Neuherberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany.; Medical Faculty, Technical University of Munich, Munich, Germany., Sterr M; Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, Neuherberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany., Böttcher A; Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, Neuherberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany., Migliorini A; Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, Neuherberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany.; McEwen Stem Cell Institute, University Health Network (UHN), Toronto, Ontario, Canada., Lickert H; Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, Neuherberg, Germany. heiko.lickert@helmholtz-muenchen.de.; German Center for Diabetes Research (DZD), Neuherberg, Germany. heiko.lickert@helmholtz-muenchen.de.; Medical Faculty, Technical University of Munich, Munich, Germany. heiko.lickert@helmholtz-muenchen.de., Theis FJ; Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany. fabian.theis@helmholtz-muenchen.de.; TUM School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany. fabian.theis@helmholtz-muenchen.de.; Department of Mathematics, Technical University of Munich, Garching, Germany. fabian.theis@helmholtz-muenchen.de.
Jazyk: angličtina
Zdroj: Nature metabolism [Nat Metab] 2023 Sep; Vol. 5 (9), pp. 1615-1637. Date of Electronic Publication: 2023 Sep 11.
DOI: 10.1038/s42255-023-00876-x
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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