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Transcriptional changes underlying progression from islet autoantibody positivity to type 1 diabetes

ABSTRACT: Transcriptional changes underlying progression from islet autoantibody positivity to type 1 diabetes

PROVIDER: PRJNA767893 | ENA |

REPOSITORIES: ENA

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Transcriptomic changes underlying progression from islet autoantibody positivity to type 1 diabetes

Project description:Transcriptomic changes underlying progression from islet autoantibody positivity to type 1 diabetes

| PRJNA739213 | ENA

Chromatin accessibility changes underlying progression from islet autoantibody positivity to type 1 diabetes

Project description:Chromatin accessibility changes underlying progression from islet autoantibody positivity to type 1 diabetes

| PRJNA739214 | ENA

Chromatin accessibility changes underlying progression from islet autoantibody positivity to type 1 diabetes

Project description:Chromatin accessibility changes underlying progression from islet autoantibody positivity to type 1 diabetes

| PRJNA767892 | ENA

Chromatin accessibility changes underlying progression from islet autoantibody positivity to type 1 diabetes

Project description:Type 1 diabetes (T1D) usually has a preclinical phase identified by the presence of circulating autoantibodies to pancreatic islet antigens, and most young children who have multiple autoantibodies progress to diabetes within 10 years. While autoantibodies denote underlying islet autoimmunity, how this process is initiated and then progresses to clinical diabetes on a background of genetic susceptibility is not clearly understood. Only one study has thus far reported changes in gene expression in isolated immune cells associated with progression to islet autoimmunity. We analysed chromatin accessibility by ATAC-seq in CD4+ T cells in four genetically at-risk children with islet autoantibodies who progressed to diabetes in ≤ 3 years (‘progressors’), compared to five at-risk children matched for sex, age and HLA who had not progressed (‘non-progressors). From ATAC-seq data, we generated the first map of chromatin accessibility in T cells of islet autoantibody-positive children. Progression was associated with a subtle reconfiguration of regulatory chromatin regions, and some of the chromatin conformation changes could be linked to progression associated expression changes at cytotoxic genes.

2022-03-09 | GSE185189 | GEO

Chromatin accessibility changes underlying progression from islet autoantibody positivity to type 1 diabetes

Project description:Type 1 diabetes (T1D) usually has a preclinical phase identified by the presence of circulating autoantibodies to pancreatic islet antigens, and most young children who have multiple autoantibodies progress to diabetes within 10 years. While autoantibodies denote underlying islet autoimmunity, how this process is initiated and then progresses to clinical diabetes on a background of genetic susceptibility is not clearly understood. Only one study has thus far reported changes in gene expression in isolated immune cells associated with progression to islet autoimmunity. We analysed gene expression and chromatin accessibility by ATAC-seq in CD4+ T cells in four genetically at-risk children with islet autoantibodies who progressed to diabetes in ≤ 3 years (‘progressors’), compared to five at-risk children matched for sex, age and HLA who had not progressed (‘non-progressors). In progressors, differentially expressed genes (DEGs) were enriched for cytotoxic genes/pathways and CD4+ TEMRA-like expression signatures. From ATAC-seq data, we generated the first map of chromatin accessibility in T cells of islet autoantibody-positive children. Progression was associated with a subtle reconfiguration of regulatory chromatin regions, and some of the chromatin conformation changes could be linked to progression associated expression changes at cytotoxic genes. In summary, our findings highlight a role for cytotoxic CD4+ T cells in progressive islet immunopathology, and suggest that some of the alterations in chromatin accessibility could underly progression associated gene expression changes

2026-06-17 | GSE178492 | GEO

Chromatin accessibility and transcriptomic changes underlying progression from islet autoantibody positivity to type 1 diabetes

Project description:Chromatin accessibility and transcriptomic changes underlying progression from islet autoantibody positivity to type 1 diabetes

| PRJNA739211 | ENA

Transcriptional and chromatin accessibility changes underlying progression from islet autoantibody positivity to type 1 diabetes

Project description:Transcriptional and chromatin accessibility changes underlying progression from islet autoantibody positivity to type 1 diabetes

| PRJNA767889 | ENA

Transcriptional changes underlying progression from islet autoantibody positivity to type 1 diabetes

2022-03-09 | GSE185190 | GEO

Transcriptomic changes underlying progression from islet autoantibody positivity to type 1 diabetes

Project description:In this study, we we collected RNA-seq data from four different human immune cells (CD4+ T cells, CD8+ T cells, B cells, NK ) to assess gene expression changes during type 1 diabetes (T1D) disease progression

2026-06-17 | GSE178493 | GEO

Circulating Metabolites in Progression to Islet Autoimmunity and Type 1 Diabetes

Project description:<h4><strong>AIMS/HYPOTHESIS: </strong>Metabolic dysregulation may precede the onset of type 1 diabetes. However, these metabolic disturbances and their specific role in disease initiation remain poorly understood. In this study, we examined whether children who progress to type 1 diabetes have a circulatory polar metabolite profile distinct from that of children who later progress to islet autoimmunity but not type 1 diabetes and a matched control group.</h4><h4><strong>METHODS: </strong>We analysed polar metabolites from 415 longitudinal plasma samples in a prospective cohort of children in three study groups: those who progressed to type 1 diabetes; those who seroconverted to one islet autoantibody but not to type 1 diabetes; and an antibody-negative control group. Metabolites were measured using two-dimensional GC high-speed time of flight MS.</h4><h4><strong>RESULTS: </strong>In early infancy, progression to type 1 diabetes was associated with downregulated amino acids, sugar derivatives and fatty acids, including catabolites of microbial origin, compared with the control group. Methionine remained persistently upregulated in those progressing to type 1 diabetes compared with the control group and those who seroconverted to one islet autoantibody. The appearance of islet autoantibodies was associated with decreased glutamic and aspartic acids.</h4><h4><strong>CONCLUSIONS/INTERPRETATION: </strong>Our findings suggest that children who progress to type 1 diabetes have a unique metabolic profile, which is, however, altered with the appearance of islet autoantibodies. Our findings may assist with early prediction of the disease.</h4>

2022-01-19 | MTBLS802 | MetaboLights

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