METHODS: Submandibular gland tissue bulk RNAseq analysis of 45 cases with a definite diagnosis of IgG4-RD was integrated with Visium spatial transcriptome analysis of 2 cases to identify pathogenic genes expressed in tertiary lymphoid tissues.
RESULTS: Bulk RNAseq and pathway analyses showed upregulation of cell cycle and T cell-related signals in IgG4-RD. Spatial transcriptome analysis identified the cluster corresponding to germinal centers and the top 38 common genes that showed significant variations in expression compared with other clusters. The top 20 genes were extracted by comparing the bulk RNAseq data. Network analysis identified CDK1 as the ge most strongly associated of the top 20 genes.
CONCLUSIONS: The CDK1 gene may be a regulator of the pathogenesis of IgG4-RD and provide clues for drug discovery.
方法:对45例明确诊断为IgG4-RD的颌下腺组织大块RNAseq分析与2例Visium空间转录组分析相结合,以鉴定在三级淋巴组织中表达的致病基因。
结果:大量RNAseq和通路分析显示IgG4-RD中细胞周期和T细胞相关信号上调。空间转录组分析确定了对应于生发中心的簇和与其他簇相比在表达上显示显著差异的前38个常见基因。通过比较大量RNAseq数据来提取前20个基因。网络分析确定CDK1是前20个基因中最密切相关的基因。
结论:CDK1基因可能是IgG4-RD发病的调节因子,为药物发现提供了线索。