We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Systematic immune cell dysregulation and molecular subtypes revealed by single-cell RNA-seq of subjects with type 1 diabetes.
- Authors
Honardoost, Mohammad Amin; Adinatha, Andreas; Schmidt, Florian; Ranjan, Bobby; Ghaeidamini, Maryam; Arul Rayan, Nirmala; Gek Liang Lim, Michelle; Joanito, Ignasius; Xiao Xuan Lin, Quy; Rajagopalan, Deepa; Qi Mok, Shi; Hwang, You Yi; Larbi, Anis; Khor, Chiea Chuen; Foo, Roger; Boehm, Bernhard Otto; Prabhakar, Shyam
- Abstract
Background: Type 1 diabetes mellitus (T1DM) is a prototypic endocrine autoimmune disease resulting from an immune-mediated destruction of pancreatic insulin-secreting β cells. A comprehensive immune cell phenotype evaluation in T1DM has not been performed thus far at the single-cell level. Methods: In this cross-sectional analysis, we generated a single-cell transcriptomic dataset of peripheral blood mononuclear cells (PBMCs) from 46 manifest T1DM (stage 3) cases and 31 matched controls. Results: We surprisingly detected profound alterations in circulatory immune cells (1784 dysregulated genes in 13 immune cell types), far exceeding the count in the comparator systemic autoimmune disease SLE. Genes upregulated in T1DM were involved in WNT signaling, interferon signaling and migration of T/NK cells, antigen presentation by B cells, and monocyte activation. A significant fraction of these differentially expressed genes were also altered in T1DM pancreatic islets. We used the single-cell data to construct a T1DM metagene z-score (TMZ score) that distinguished cases and controls and classified patients into molecular subtypes. This score correlated with known prognostic immune markers of T1DM, as well as with drug response in clinical trials. Conclusions: Our study reveals a surprisingly strong systemic dimension at the level of immune cell network in T1DM, defines disease-relevant molecular subtypes, and has the potential to guide non-invasive test development and patient stratification.
- Subjects
TYPE 1 diabetes; MONONUCLEAR leukocytes; B cell receptors; ANTIGEN presentation; BIOMARKERS; RNA sequencing
- Publication
Genome Medicine, 2024, Vol 16, Issue 1, p1
- ISSN
1756-994X
- Publication type
Article
- DOI
10.1186/s13073-024-01300-z