整合单细胞 RNA-Seq 和 ATAC-Seq 分析强直性脊柱炎患者外周血单核细胞。
Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Peripheral Mononuclear Cells in Patients With Ankylosing Spondylitis.
机构信息
Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen Engineering Research Center of Autoimmune Disease, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, China.
Department of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
出版信息
Front Immunol. 2021 Nov 22;12:760381. doi: 10.3389/fimmu.2021.760381. eCollection 2021.
OBJECTIVE
Genetic studies on ankylosing spondylitis (AS) have identified more than 100 pathogenic genes. Building a bridge between these genes and biologically targeted therapies is the current research hotspot.
METHODS
We integrated single-cell assaying transposase-accessible chromatin sequencing (scATAC-seq) and single-cell RNA sequencing (scRNA-seq) to explore the key genes and related mechanisms associated with AS pathogenesis.
RESULTS
We identified 18 cell types in peripheral mononuclear cells from patients with AS and normal controls and summarized the cell-type-specific abnormal genes by scRNA-seq. Interestingly, we found that the pathogenic gene involved in AS progression originated from CD8+ T cells. Moreover, we observed an abnormal tumor TNF pathway mediated by abnormal expression of , , , , and , and scATAC-seq results confirmed the abnormal accessible binding sites of transcriptional factors , , and . The final magnetic bead sorting and quantitative real-time PCR(RT-qPCR) confirmed that , , , and in CD8+ T cells differed in the AS group.
CONCLUSIONS
Our results revealed a possible mechanism by which abnormally regulates , , and and drives progression, providing a novel perspective from a single cell point of view in AS.
目的
强直性脊柱炎（AS）的遗传研究已经确定了 100 多个致病基因。将这些基因与生物靶向治疗联系起来是当前的研究热点。
方法
我们整合了单细胞转座酶可及染色质测序（scATAC-seq）和单细胞 RNA 测序（scRNA-seq），以探索与 AS 发病机制相关的关键基因和相关机制。
结果
我们在 AS 患者和正常对照的外周血单核细胞中鉴定出 18 种细胞类型，并通过 scRNA-seq 总结了细胞类型特异性异常基因。有趣的是，我们发现参与 AS 进展的致病基因源于 CD8+T 细胞。此外，我们观察到肿瘤 TNF 途径异常，由 、 、 、 和 异常表达介导，scATAC-seq 结果证实了转录因子 、 和 的异常可及结合位点。最终的磁珠分选和定量实时 PCR（RT-qPCR）证实，AS 组 CD8+T 细胞中的 、 、 和 存在差异。
结论
我们的研究结果揭示了一种可能的机制，即 异常调节 、 、 和 ，并驱动 进展，从单细胞角度为 AS 提供了一个新的视角。
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