Ye Xiangyu, Wei Julong, Yue Ming, Wang Yan, Chen Hongbo, Zhang Yongfeng, Wang Yifan, Zhang Meiling, Huang Peng, Yu Rongbin
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, United States.
Front Genet. 2021 Mar 8;12:637322. doi: 10.3389/fgene.2021.637322. eCollection 2021.
Components of liver microenvironment is complex, which makes it difficult to clarify pathogenesis of chronic liver diseases (CLD). Genome-wide association studies (GWASs) have greatly revealed the role of host genetic background in CLD pathogenesis and prognosis, while single-cell RNA sequencing (scRNA-seq) enables interrogation of the cellular diversity and function of liver tissue at unprecedented resolution. Here, we made integrative analysis on the GWAS and scRNA-seq data of CLD to uncover CLD-related cell types and provide clues for understanding on the pathogenesis.
We downloaded three GWAS summary data and three scRNA-seq data on CLD. After defining the cell types for each scRNA-seq data, we used and to integrate the GWAS and scRNA-seq. In addition, we analyzed one scRNA-seq data without association to CLD to validate the specificity of our findings.
After processing the scRNA-seq data, we obtain about 19,002-32,200 cells and identified 10-17 cell types. For the HCC analysis, we identified the association between B cell and HCC in two datasets. also identified the association, when we integrated the two scRNA-seq datasets. In addition, we also identified natural killer (NK) cell as HCC-associated cell type in one dataset. In specificity analysis, we identified no significant cell type associated with HCC. As for the cirrhosis analysis, we obtained no significant related cell type.
In this integrative analysis, we identified B cell and NK cell as HCC-related cell type. More attention and verification should be paid to them in future research.
肝脏微环境的组成复杂，这使得阐明慢性肝病（CLD）的发病机制变得困难。全基因组关联研究（GWAS）极大地揭示了宿主遗传背景在CLD发病机制和预后中的作用，而单细胞RNA测序（scRNA-seq）能够以前所未有的分辨率探究肝脏组织的细胞多样性和功能。在此，我们对CLD的GWAS和scRNA-seq数据进行综合分析，以揭示与CLD相关的细胞类型，并为理解发病机制提供线索。
我们下载了三个关于CLD的GWAS汇总数据和三个scRNA-seq数据。在为每个scRNA-seq数据定义细胞类型后，我们使用[具体方法1]和[具体方法2]来整合GWAS和scRNA-seq。此外，我们分析了一个与CLD无关的scRNA-seq数据，以验证我们发现的特异性。
在处理scRNA-seq数据后，我们获得了约19,002 - 32,200个细胞，并鉴定出10 - 17种细胞类型。对于肝癌（HCC）分析，我们在两个数据集中确定了B细胞与HCC之间的关联。当我们整合两个scRNA-seq数据集时，[具体方法2]也确定了这种关联。此外，我们还在一个数据集中将自然杀伤（NK）细胞鉴定为与HCC相关的细胞类型。在特异性分析中，我们未发现与HCC相关的显著细胞类型。至于肝硬化分析，我们未获得显著相关的细胞类型。
在这项综合分析中，我们将B细胞和NK细胞鉴定为与HCC相关的细胞类型。在未来的研究中应给予它们更多关注并进行验证。
