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Publication : Delineating mouse ??-cell identity during lifetime and in diabetes with a single cell atlas.

First Author  Hrovatin K Year  2023
Journal  Nat Metab Volume  5
Issue  9 Pages  1615-1637
PubMed ID  37697055 Mgi Jnum  J:385689
Mgi Id  MGI:8163592 Doi  10.1038/s42255-023-00876-x
Citation  Hrovatin K, et al. (2023) Delineating mouse beta-cell identity during lifetime and in diabetes with a single cell atlas. Nat Metab 5(9):1615-1637
abstractText  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 beta-cell ablation model. The beta-cell landscape of MIA reveals new cell states during disease progression and cross-publication differences between previously suggested marker genes. We show that beta-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 beta-cells. We also report pathways that are shared between beta-cells in immature, aged and diabetes models. MIA enables a comprehensive analysis of beta-cell responses to different stressors, providing a roadmap for the understanding of beta-cell plasticity, compensation and demise.
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