Journal Article

DZNE-2023-00958

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Delineating mouse β-cell identity during lifetime and in diabetes with a single cell atlas.

Hrovatin, K. ; Bastidas-Ponce, A. ; Bakhti, M. ; Zappia, L. ; Buettner, M.DZNE* ; Salinno, C. ; Sterr, M. ; Böttcher, A. ; Migliorini, A. ; Lickert, H. ; Theis, F. J.

2023
Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s42255-023-00876-x

Abstract: 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.

Keyword(s): Humans (MeSH) ; Animals (MeSH) ; Mice (MeSH) ; Aged (MeSH) ; Mice, Inbred NOD (MeSH) ; Diabetes Mellitus, Type 1: genetics (MeSH) ; Diabetes Mellitus, Type 2: genetics (MeSH) ; Streptozocin (MeSH) ; Disease Models, Animal (MeSH) ; Streptozocin

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Contributing Institute(s):

1. Clinical Single Cell Omics (CSCO) / Systems Medicine (AG Schultze)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2023

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Nature ; Essential Science Indicators ; IF >= 20 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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