Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen Engineering Research Center of Autoimmune Diseases, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong, 518020, People's Republic of China.
Guangxi Key Laboratory of Metabolic Diseases Research, Guilin Key Laboratory of Kidney Diseases Research, 924st Hospital Guilin, Guangxi, 541002, Guilin, People's Republic of China.
Clin Rheumatol. 2022 Nov;41(11):3513-3524. doi: 10.1007/s10067-022-06310-z. Epub 2022 Jul 29.
This study aims to provide a new perspective of determining the pathophysiology of chronic hepatitis B (CHB) development by analyzing the gene regulatory network in CHB patients using single-cell ATAC sequencing.
Hepatitis B virus (HBV)-related liver disease induces liver damage by hepatic immune and inflammatory responses. The exact mechanism is unknown. As such, there is an urgent need to address this problem and study the relationship between aberrant peripheral blood mononuclear cell (PBMC) immune response and progression of liver disease.
The sequencing of the chromatin accessibility of 8016 cells from the whole venous blood of normal control (NC) individuals and CHB patients was performed through assay for transposase-accessible chromatin in single-cell sequencing (ScATAC-seq). Unsupervised clustering and annotation analyses were performed by Signac (version 1.7.0) and Seurat clustering to identify different cell types. Then, TF motif enrichment analysis and differentially expressed peak analysis were performed to identify cell-type-specific candidate open chromatins related to CHB.
We identified 12 leukocytic clusters corresponding to five cell types. The specific cell types associated with CHB were found to be located in B-0 and T-3. We have drawn the regulatory network of the hepatitis B signal pathway composed of genes linked to the differentially expressed peaks of these two CHB disease-specific cell types. Further, we profoundly explored the potential mechanisms of B-0-associated TF motif IRF2 and T-3-associated TF motif FOXC2 in the occurrence of CHB.
We have drawn a systematic and distinguishing gene regulatory network of CHB-related PBMCs. Key Points • Peripheral blood mononuclear cells were robustly clustered based on their types without using antibodies. • We draw a systematic and distinctive gene regulatory network of CHB-related PBMC through ScATAC-seq.
通过单细胞 ATAC 测序分析 CHB 患者的基因调控网络，为确定慢性乙型肝炎（CHB）发展的病理生理学提供新视角。
乙型肝炎病毒（HBV）相关肝病通过肝免疫和炎症反应引起肝损伤。确切的机制尚不清楚。因此，迫切需要解决这一问题，并研究异常外周血单个核细胞（PBMC）免疫反应与肝病进展的关系。
通过单细胞测序（ScATAC-seq）对 8016 个正常对照（NC）个体和 CHB 患者全静脉血的染色质可及性进行测序。通过 Signac（版本 1.7.0）和 Seurat 聚类进行无监督聚类和注释分析，以识别不同的细胞类型。然后，进行 TF 基序富集分析和差异表达峰分析，以鉴定与 CHB 相关的细胞类型特异性候选开放染色质。
我们鉴定了 12 个对应于 5 种细胞类型的白细胞簇。与 CHB 相关的特定细胞类型被发现位于 B-0 和 T-3 中。我们构建了由与这两种 CHB 疾病特异性细胞类型差异表达峰相关的基因组成的乙型肝炎信号通路调控网络。此外，我们还深入探讨了 B-0 相关 TF 基序 IRF2 和 T-3 相关 TF 基序 FOXC2 在 CHB 发生中的潜在机制。
我们绘制了 CHB 相关 PBMC 的系统和有区别的基因调控网络。
无需使用抗体即可根据细胞类型对单核细胞进行稳健聚类。
通过 ScATAC-seq 绘制了 CHB 相关 PBMC 的系统和独特的基因调控网络。
