ATAC-seq和RNA-seq的综合分析揭示了免疫球蛋白肾病的染色质可及性和转录景观。

IF 4.5 3区医学 Q2 IMMUNOLOGY

Clinical immunology Pub Date : 2025-01-21 DOI:10.1016/j.clim.2025.110432

Zhao-Xing Gao , Yang Fang , Shu-Zhen Xu , Yi-Sheng He , Man Ge , Peng Zhang , Yi-Qing Xu , Tian He , Peng Wang , De-Guang Wang , Hai-Feng Pan

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引用次数: 0

摘要

背景：CD4+ T细胞染色质可及性与免疫球蛋白A肾病（IgAN）之间的关系尚不清楚。方法：对CD4+ T细胞进行转座酶可及染色质测序（ATAC-seq）和RNA测序（RNA-seq）测定。通过ATAC-seq和RNA-seq分别鉴定差异可达区和差异表达基因（DEGs）（P 1）。采用QRT-PCR验证靶基因表达。结果：共鉴定出100,865个可达性差异区域，其中7225个区域具有较高的可达性。功能分析显示，这些区域在T淋巴细胞活化和免疫途径中富集。ELF3、MEIS1和NFYC被确定为与IgAN相关的关键tf。QRT-PCR显示IgAN中包括MEIS1在内的枢纽基因显著上调。结论：通过整合ATAC-seq和RNA-seq，我们发现了IgAN的关键tf和基因，为IgAN的治疗提供了新的靶点，并从表观遗传学的角度了解了IgAN的发病机制。

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Integrated analysis of ATAC-seq and RNA-seq reveals the chromatin accessibility and transcriptional landscape of immunoglobulin a nephropathy

Backgrounds

The association between chromatin accessibility in CD4⁺ T cells and Immunoglobulin A nephropathy (IgAN) remains unclear.

Methods

We performed the assay for transposase accessible chromatin with sequencing (ATAC-seq) and RNA sequencing (RNA-seq) on CD4⁺ T cells. ATAC-seq and RNA-seq were conducted to identify differentially accessible regions and differentially expressed genes (DEGs), respectively (P < 0.05, |log2 Fold Change| >1). QRT-PCR was utilized to validate target gene expression.

Results

We identified 100,865 differentially accessible regions, of which 7225 exhibited higher accessibility in IgAN. Functional analysis revealed that these regions are enriched in T lymphocyte activation and immune pathways. ELF3, MEIS1, and NFYC were identified as key TFs associated with IgAN. QRT-PCR indicated a significant upregulation of hub genes including MEIS1 in IgAN.

Conclusion

We identified key TFs and genes by integrating ATAC-seq and RNA-seq, which provide novel therapeutic targets for IgAN and insights into its pathogenesis from an epigenetic perspective.

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来源期刊

Clinical immunology 医学-免疫学

CiteScore

12.30

自引率

1.20%

发文量

212

审稿时长

34 days

期刊介绍： Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.