analysis-based-on-tcga-data-single-cell-data-taking-trpm4-as-an

Analysis Based on TCGA Data and Single-cell Data, taking <em>TRPM4</em> as an Example

In this article, an analysis method is introduced based on public transcriptomic datasets and single-cell datasets, which could be used to comprehensively ...

Nanjing Medical University

To investigate the association between polymorphisms in PTPN2 (rs1893217 and rs478582) and type 1 diabetes (T1D) risk with different diagnosed age, as well as related clinical characteristics in Chinese Han population.

The association between rs1893217, rs478582 in PTPN2 and T1D risk with different diagnosed age, and related clinical characteristics in Chinese Han population.

Recent meta-genome-wide association studies identified several genetic variants associated with beta-cell function in type 1 diabetes (T1D). The aim of this study was to investigate the associations between these variants and T1D risk, C-peptide levels, islet-specific autoantibodies, and lipid levels in Chinese Han population.

The associations between three genome-wide risk variants for serum C-peptide of T1D and autoantibody-positive T1D risk, and clinical characteristics in Chinese population.

CD4 Tregs are involved in the regulation of various autoimmune diseases but believed to be highly heterogeneous. Studies have indicated that Helios controls a distinct subset of functional Tregs. However, the immunological changes in circulating Helios and Helios Tregs are not fully explored in type 1 diabetes (T1D). Here, we elucidated the differences in maturation status and immune regulatory phenotypes of Helios and Helios Tregs and their correlations with monocyte subsets in T1D individuals. As CD25 FOXP3 Tregs also represent a subset of functional Tregs, we defined Tregs as FOXP3CD127 and examined circulating Helios and Helios Treg subpopulations in 68 autoantibody-positive T1D individuals and 68 age-matched healthy controls. We found that expression of both FOXP3 and CTLA4 diminished in Helios Tregs, while the proportion of CD25 Tregs increased in Helios Tregs of T1D individuals. Although the frequencies of neither Helios nor Helios Tregs were affected by investigated T1D genetic risk loci, Helios Tregs correlated with age at T1D diagnosis negatively and disease duration positively. Moreover, the negative correlation between central and effector memory proportions of Helios Tregs in healthy controls was disrupted in T1D individuals. Finally, regulatory non-classical and intermediate monocytes also decreased in T1D individuals, and positive correlations between these regulatory monocytes and Helios/Helios Treg subsets in healthy controls disappeared in T1D individuals. In conclusion, we demonstrated the alternations in maturation status and immune phenotypes in Helios and Helios Treg subsets and revealed the missing association between these Treg subsets and monocyte subsets in T1D individuals, which might point out another option for elucidating T1D mechanisms.

Differences in Maturation Status and Immune Phenotypes of Circulating Helios and Helios Tregs and Their Disrupted Correlations With Monocyte Subsets in Autoantibody-Positive T1D Individuals.

Circulating CD25 B cells, a subset of regulatory B cells in humans, are closely related to inflammation and autoimmune diseases. This study is aimed at investigating the alternation of CD25 Bregs and their correlation with CD4 effector and regulatory T cells in T1D individuals. We included 68 autoantibody-positive T1D and 68 age-matched healthy individuals with peripheral blood mononuclear cells (PBMCs) and assessed them with CD25 Bregs and CD4 effector or regulatory T cells by flow cytometry. Here, we demonstrate that the frequency of CD25 Bregs was significantly decreased in T1D subjects ( = 0.0016), but they were not affected by disease status (age at T1D diagnosis or duration) or T1D risk loci (rs2104286 or rs12251307) in  (all  > 0.05). Moreover, higher IgD ( = 0.043) and lower CD27 ( = 0.0003) expression was observed in CD25 Bregs of T1D individuals, but not the expression of IgM, CD24, or CD38 (all  > 0.05). Although there was no correlation between CD25 Bregs and CD4 effector T cell subsets in either T1D or healthy individuals (all  > 0.05), we found a positive correlation between CD25 Bregs and CD4 Tregs in healthy controls (Sp.  = 0.3544,  = 0.0249), which disappeared in T1D subjects (Sp.  = 0.137,  = 0.401). In conclusion, our results suggest that decreased CD25 Bregs and alternation of their phenotypes are features of T1D regardless of disease duration and T1D genetic risk loci, and an impaired balance between CD25 Bregs and CD4 Tregs might contribute to the pathogenesis of T1D.

Differences of Circulating CD25 Bregs and Their Correlations with CD4 Effector and Regulatory T Cells in Autoantibody-Positive T1D Compared with Age-Matched Healthy Individuals.

Our previous genome‑wide association studies (GWAS) have suggested rs912304 in 14q12 as a suggestive risk variant for type 1 diabetes (T1D). However, the association between this risk region and T1D subgroups and related clinical risk features, the underlying causal functional variant(s), putative candidate gene(s), and related mechanisms are yet to be elucidated.

A functional variant rs912304 for late-onset T1D risk contributes to islet dysfunction by regulating proinflammatory cytokine-responsive gene STXBP6 expression.

Bladder cancer (BLCA) is one of the most invasive and malignant tumors in the world, thus leading to the urgent need of an accurate and recognizable biomarker. Several previous research has shown that Transient Receptor Potential Melastatin 4 (TRPM4) plays an important role in measuring vascular fragility and endothelial function. However, the role of TRPM4 in tumor hasn't been explored.

Article	Year
The association between rs1893217, rs478582 in PTPN2 and T1D risk with different diagnosed age, and related clinical characteristics in Chinese Han population. Autoimmunity\| PubMed ID: 31030572	2019
The associations between three genome-wide risk variants for serum C-peptide of T1D and autoantibody-positive T1D risk, and clinical characteristics in Chinese population. Journal of human genetics\| PubMed ID: 31827251	2020
Differences in Maturation Status and Immune Phenotypes of Circulating Helios and Helios Tregs and Their Disrupted Correlations With Monocyte Subsets in Autoantibody-Positive T1D Individuals. Frontiers in immunology\| PubMed ID: 34054801	2021
Differences of Circulating CD25 Bregs and Their Correlations with CD4 Effector and Regulatory T Cells in Autoantibody-Positive T1D Compared with Age-Matched Healthy Individuals. Journal of immunology research\| PubMed ID: 35083339	2022
A functional variant rs912304 for late-onset T1D risk contributes to islet dysfunction by regulating proinflammatory cytokine-responsive gene STXBP6 expression. BMC medicine\| PubMed ID: 39227839	2024
Transient Receptor Potential Melastatin 4 (TRPM4) is associated with an immuno-stimulatory TME and better prognosis in BLCA. Discover oncology\| PubMed ID: 41266683	2025

Yuyue Zhang

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