An Early Islet Transcriptional Signature Is Associated With Local Inflammation in Autoimmune Diabetes
AuthorsDerr, Alan G
Redick, Sambra D
Trombly, Melanie I
Baer, Christina E
Harlan, David M
Greiner, Dale L
Wang, Jennifer P
UMass Chan AffiliationsDiabetes Center of Excellence
Microbiology and Physiological Systems
Morningside Graduate School of Biomedical Sciences
Program in Bioinformatics and Integrative Biology
Program in Molecular Medicine
Document TypeJournal Article
MetadataShow full item record
AbstractIdentifying the early islet cellular processes of autoimmune type 1 diabetes (T1D) in humans is challenging given the absence of symptoms during this period and the inaccessibility of the pancreas for sampling. In this article, we study temporal events in pancreatic islets in LEW.1WR1 rats, in which autoimmune diabetes can be induced with virus infection, by performing transcriptional analysis of islets harvested during the prediabetic period. Single-cell RNA-sequencing and differential expression analyses of islets from prediabetic rats reveal subsets of β- and α-cells under stress as evidenced by heightened expression, over time, of a transcriptional signature characterized by interferon-stimulated genes, chemokines including Cxcl10, major histocompatibility class I, and genes for the ubiquitin-proteasome system. Mononuclear phagocytes show increased expression of inflammatory markers. RNA-in situ hybridization of rat pancreatic tissue defines the spatial distribution of Cxcl10+ β- and α-cells and their association with CD8+ T cell infiltration, a hallmark of insulitis and islet destruction. Our studies define early islet transcriptional events during immune cell recruitment to islets and reveal spatial associations between stressed β- and α-cells and immune cells. Insights into such early processes can assist in the development of therapeutic and prevention strategies for T1D.
SourceDerr AG, Arowosegbe A, Satish B, Redick SD, Qaisar N, Guo Z, Vanderleeden E, Trombly MI, Baer CE, Harlan DM, Greiner DL, Garber M, Wang JP. An Early Islet Transcriptional Signature Is Associated With Local Inflammation in Autoimmune Diabetes. Diabetes. 2023 Feb 1;72(2):261-274. doi: 10.2337/db22-0521. PMID: 36346618; PMCID: PMC9871196.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/51966
Rights© 2023 by the American Diabetes Association.