PuSH - Publikationsserver des Helmholtz Zentrums München

Gottmann, P.* ; Speckmann, T.* ; Stadion, M.* ; Chawla, P.* ; Saurenbach, J.* ; Ninov, N.* ; Lickert, H. ; Schürmann, A.*

Transcriptomic heterogeneity of non-beta islet cells is associated with type 2 diabetes development in mouse models.

Diabetologia, DOI: 10.1007/s00125-024-06301-6 (2024)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
AIMS/HYPOTHESIS: The aim of this work was to understand the role of non-beta cells in pancreatic islets at early stages of type 2 diabetes pathogenesis. METHODS: Specific clustering was employed to single-cell transcriptome data from islet cells of obese mouse strains differing in their diabetes susceptibility (diabetes-resistant B6.V.Lepob/ob [OB] and diabetes-susceptible New Zealand Obese [NZO] mice) on a diabetogenic diet. RESULTS: Refined clustering analysis revealed several heterogeneous subpopulations for alpha cells, delta cells and macrophages, of which 133 mapped to human diabetes genes identified by genome-wide association studies. Importantly, a similar non-beta cell heterogeneity was found in a dataset of human islets from donors at different stages of type 2 diabetes. The predominant alpha cell cluster in NZO mice displayed signs of cellular stress and lower mitochondrial capacity (97 differentially expressed genes [DEGs]), whereas delta cells from these mice exhibited higher expression levels of maturation marker genes (Hhex and Sst) but lower somatostatin secretion than OB mice (184 DEGs). Furthermore, a cluster of macrophages was almost twice as abundant in islets of OB mice, and displayed extensive cell-cell communication with beta cells of OB mice. Treatment of beta cells with IL-15, predicted to be released by macrophages, activated signal transducer and activator of transcription (STAT3), which may mediate anti-apoptotic effects. Similar to mice, humans without diabetes possess a greater number of macrophages than those with prediabetes (39 mmol/mol [5.7%] < HbA1c < 46 mmol/mol [6.4%]) and diabetes. CONCLUSIONS/INTERPRETATION: Our study indicates that the transcriptional heterogeneity of non-beta cells has an impact on intra-islet crosstalk and participates in beta cell (dys)function. DATA AVAILABILITY: scRNA-seq data from the previous study are available in gene expression omnibus under gene accession number GSE159211 ( https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE159211 ).
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Beta Cell Protection ; Cell–cell Communication ; Heterogeneity In Islets ; Macrophages ; Type 2 Diabetes; Pancreatic-islets; Macrophages; Insulin; Dysfunction; Proliferation; Inflammation; Obesity; Secretion; Resistant; Release
ISSN (print) / ISBN 0012-186X
e-ISSN 1432-0428
Zeitschrift Diabetologia
Verlag Springer
Verlagsort Berlin ; Heidelberg [u.a.]
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Regeneration Research (IDR)
Institute of Stem Cell Research (ISF)
Förderungen Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
Brandenburg State
German Ministry of Education and Research (BMBF: DZD)
Projekt DEAL