Differentially Expressed Micro-RNAs as Biomarkers for Prediction and Prognosis in Autoimmune Type 1 Diabetes.

2014 ◽  
Vol 98 ◽  
pp. 905
Author(s):  
P. Chhabra ◽  
R. Gehrau ◽  
J. Hansen ◽  
V. Mas ◽  
K. Brayman
2019 ◽  
Vol 20 (23) ◽  
pp. 5903 ◽  
Author(s):  
Preethi Krishnan ◽  
Farooq Syed ◽  
Nicole Jiyun Kang ◽  
Raghavendra G. Mirmira ◽  
Carmella Evans-Molina

Type 1 diabetes (T1D) is characterized by the immune-mediated destruction of insulin-producing islet β cells. Biomarkers capable of identifying T1D risk and dissecting disease-related heterogeneity represent an unmet clinical need. Toward the goal of informing T1D biomarker strategies, we profiled coding and noncoding RNAs in human islet-derived exosomes and identified RNAs that were differentially expressed under proinflammatory cytokine stress conditions. Human pancreatic islets were obtained from cadaveric donors and treated with/without IL-1β and IFN-γ. Total RNA and small RNA sequencing were performed from islet-derived exosomes to identify mRNAs, long noncoding RNAs, and small noncoding RNAs. RNAs with a fold change ≥1.3 and a p-value <0.05 were considered as differentially expressed. mRNAs and miRNAs represented the most abundant long and small RNA species, respectively. Each of the RNA species showed altered expression patterns with cytokine treatment, and differentially expressed RNAs were predicted to be involved in insulin secretion, calcium signaling, necrosis, and apoptosis. Taken together, our data identify RNAs that are dysregulated under cytokine stress in human islet-derived exosomes, providing a comprehensive catalog of protein coding and noncoding RNAs that may serve as potential circulating biomarkers in T1D.


Diabetes ◽  
2022 ◽  
Author(s):  
Naiara G. Bediaga ◽  
Alexandra L. Garnham ◽  
Gaetano Naselli ◽  
Esther Bandala-Sanchez ◽  
Natalie L. Stone ◽  
...  

Type 1 diabetes in children is heralded by a preclinical phase defined by circulating autoantibodies to pancreatic islet antigens. How islet autoimmunity is initiated and then progresses to clinical diabetes remains poorly understood. Only one study has reported gene expression in specific immune cells of at-risk children, associated with progression to islet autoimmunity. We analysed gene expression by RNAseq in CD4+ and CD8+ T cells, NK cells and B cells, and chromatin accessibility by ATACseq in CD4+ T cells, in five genetically at-risk children with islet autoantibodies who progressed to diabetes over a median of 3 years (‘Progressors’) compared to five children matched for sex, age and HLA-DR who had not progressed (‘Non-progressors). In Progressors, differentially expressed genes (DEGs) were largely confined to CD4+ T cells and enriched for cytotoxicity-related genes/pathways. Several top-ranked DEGs were validated in a semi-independent cohort of 13 Progressors and 11 Non-progressors. Flow cytometry confirmed progression was associated with expansion of CD4+ cells with a cytotoxic phenotype. By ATAC-seq, progression was associated with reconfiguration of regulatory chromatin regions in CD4+ T cells, some linked to differentially expressed cytotoxicity-related genes. Our findings suggest that cytotoxic CD4+ T cells play a role in promoting progression to type 1 diabetes.


2022 ◽  
Author(s):  
Naiara G. Bediaga ◽  
Alexandra L. Garnham ◽  
Gaetano Naselli ◽  
Esther Bandala-Sanchez ◽  
Natalie L. Stone ◽  
...  

Type 1 diabetes in children is heralded by a preclinical phase defined by circulating autoantibodies to pancreatic islet antigens. How islet autoimmunity is initiated and then progresses to clinical diabetes remains poorly understood. Only one study has reported gene expression in specific immune cells of at-risk children, associated with progression to islet autoimmunity. We analysed gene expression by RNAseq in CD4<sup>+</sup> and CD8<sup>+</sup> T cells, NK cells and B cells, and chromatin accessibility by ATACseq in CD4<sup>+</sup> T cells, in five genetically at-risk children with islet autoantibodies who progressed to diabetes over a median of 3 years (‘Progressors’) compared to five children matched for sex, age and HLA-DR who had not progressed (‘Non-progressors). In Progressors, differentially expressed genes (DEGs) were largely confined to CD4<sup>+</sup> T cells and enriched for cytotoxicity-related genes/pathways. Several top-ranked DEGs were validated in a semi-independent cohort of 13 Progressors and 11 Non-progressors. Flow cytometry confirmed progression was associated with expansion of CD4<sup>+ </sup>cells with a cytotoxic phenotype. By ATAC-seq, progression was associated with reconfiguration of regulatory chromatin regions in CD4<sup>+ </sup>cells, some linked to differentially expressed cytotoxicity-related genes. Our findings suggest that cytotoxic CD4<sup>+ </sup>T cells play a role in promoting progression to type 1 diabetes.


2014 ◽  
Author(s):  
Carah A Figueroa-crisostomo ◽  
Ammira Sarah Akil ◽  
Andy Ho ◽  
Anand Hardikar ◽  
Ryan Farr ◽  
...  

Diabetologia ◽  
2019 ◽  
Vol 63 (1) ◽  
pp. 124-136 ◽  
Author(s):  
Giuliana Ventriglia ◽  
Francesca Mancarella ◽  
Guido Sebastiani ◽  
Dana P. Cook ◽  
Roberto Mallone ◽  
...  

2019 ◽  
Vol 10 ◽  
Author(s):  
Daniele P. Santos-Bezerra ◽  
Aritania S. Santos ◽  
Gabriel C. Guimarães ◽  
Sharon N. Admoni ◽  
Ricardo V. Perez ◽  
...  

2022 ◽  
Author(s):  
Naiara G. Bediaga ◽  
Alexandra L. Garnham ◽  
Gaetano Naselli ◽  
Esther Bandala-Sanchez ◽  
Natalie L. Stone ◽  
...  

Type 1 diabetes in children is heralded by a preclinical phase defined by circulating autoantibodies to pancreatic islet antigens. How islet autoimmunity is initiated and then progresses to clinical diabetes remains poorly understood. Only one study has reported gene expression in specific immune cells of at-risk children, associated with progression to islet autoimmunity. We analysed gene expression by RNAseq in CD4<sup>+</sup> and CD8<sup>+</sup> T cells, NK cells and B cells, and chromatin accessibility by ATACseq in CD4<sup>+</sup> T cells, in five genetically at-risk children with islet autoantibodies who progressed to diabetes over a median of 3 years (‘Progressors’) compared to five children matched for sex, age and HLA-DR who had not progressed (‘Non-progressors). In Progressors, differentially expressed genes (DEGs) were largely confined to CD4<sup>+</sup> T cells and enriched for cytotoxicity-related genes/pathways. Several top-ranked DEGs were validated in a semi-independent cohort of 13 Progressors and 11 Non-progressors. Flow cytometry confirmed progression was associated with expansion of CD4<sup>+ </sup>cells with a cytotoxic phenotype. By ATAC-seq, progression was associated with reconfiguration of regulatory chromatin regions in CD4<sup>+ </sup>cells, some linked to differentially expressed cytotoxicity-related genes. Our findings suggest that cytotoxic CD4<sup>+ </sup>T cells play a role in promoting progression to type 1 diabetes.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ruifeng Shi ◽  
Fang Dai ◽  
Yong He ◽  
Li Sun ◽  
Min Xu ◽  
...  

ObjectivesAlterations in natural killer (NK) cells activity cause damage to pancreatic islets in type 1 diabetes mellitus (T1DM). The aim of this study is to identify T1DM ketosis- or ketoacidosis-related genes in activated CD56+CD16+ NK cells.MethodsMicroarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed using the GEO2R tool. Enrichment analyses were performed using Metascape online database and GSEA software. Cell-specific gene co-expression network was built using NetworkAnalyst tools. Cytoscape software was used to identify hub genes and construct co-expressed networks. Target miRNAs were predicted based on the DIANA-micro T, miRDB, and miRWalk online databases.ResultsA total of 70 DEGs were identified between T1DM patients recovered from ketosis or ketoacidosis and healthy control blood samples in GSE44314. Among the DEGs, 10 hub genes were screened out. The mature NK cell-specific gene co-expression network for DEGs in T1DM was built using NetworkAnalyst tools. DEGs between activated CD56+CD16+ NK cells and CD56brightCD16- NK cells were identified from GSE1511. After intersection, 13 overlapping genes between GSE44314 and GSE1511 microarray datasets were screened out, in which 7 hub genes were identified. Additionally, 59 target miRNAs were predicted according to the 7 hub genes. After validating with the exosome miRNA expression profile dataset of GSE97123, seven differentially expressed miRNAs (DEmiRNAs) in plasma-derived exosome were selected. Finally, a mRNA–miRNA network was constructed, which was involved in the T1DM ketosis or ketoacidosis process.ConclusionThis work identified seven hub genes in activated CD56+CD16+ NK cells and seven miRNAs in plasma-derived exosome as potential predictors of T1DM ketoacidosis, which provided a novel insight for the pathogenesis at the transcriptome level.


2022 ◽  
Vol 12 ◽  
Author(s):  
Jianyi Lv ◽  
Yihan Liu ◽  
Jia Cui ◽  
Hongjuan Fang ◽  
Ying Wu ◽  
...  

Long noncoding RNAs (lncRNAs) have been reported to have multiple functions and can be used as markers of various diseases, including diabetes. This study was conducted to determine the lncRNA profile in leukocytes from patients with type 2 diabetes (T2D). Differential expression of lncRNAs in T2D and type 1 diabetes (T1D) was also examined. RNA sequencing was performed in a critically grouped sample of leukocytes from T2D patients and healthy persons. A total of 845 significantly differentially expressed lncRNAs were identified, with 260 downregulated and 585 upregulated lncRNAs in T2D. The analysis of functions of DE-lncRNA and constructed co-expression networks (CNC) showed that 21 lncRNAs and 117 mRNAs harbored more than 10 related genes in CNC. Fourteen of 21 lncRNAs were confirmed to be significantly differentially expressed was detected by qPCR between the T2D and control validation cohorts. We also identified a panel of 4 lncRNAs showing significant differences in expression between T1D and T2D. Collectively, hundreds of novel DE-lncRNAs we identified in leukocytes from T2D patients will aid in epigenetic mechanism studies. Fourteen confirmed DE-lncRNAs can be regarded as diagnostic markers or regulators of T2D, including 4 lncRNAs that chould distinguish T1D and T2D in clinical practice to avoid misdiagnosis.


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