Leveraging Single-Cell RNA-seq Data to Uncover the Association Between Cell Type and Chronic Liver Diseases

Ye, Xiangyu; Wei, Jian; Yue, Ming; Wang, Yan; Chen, Hongbo; Zhang, Yongfeng; Wang, Yifan; Zhang, Meiling; Huang, Peng; Yu, Rongbin

doi:10.3389/fgene.2021.637322

Cited by 4 publications

(2 citation statements)

References 50 publications

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“…scRNA-seq can provide a comprehensive understanding of the pathogenesis of HCC and is conducive to individualized treatment of HCC. Multiple studies analyzed the scRNA-seq data from healthy controls, tumor tissues and adjacent tissues, and the results showed that the difference of proportion of various immune cells, including CD8 + T cells, NK cells, macrophages, B cells and other cells (58)(59)(60)(61). The changes of infiltrated immune cells may be related to the immunosuppressive microenvironment in HCC and correlated with HCC progression (62).…”

Section: Discussionmentioning

confidence: 99%

Peripheral immune characteristics of hepatitis B virus-related hepatocellular carcinoma

Sun

Lin

et al. 2023

Front. Immunol.

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BackgroundLiver cancer is the sixth most common cancer worldwide and the third leading cause of cancer-related death. As a chronic liver disease, many studies have shown that the immune response plays a key role in the progression of liver cancer. Chronic hepatitis B virus (HBV) infection is one of the high-risk factors for HCC, accounting for 50%–80% of HCC cases worldwide, and little is known about the immune status of HBV associated hepatocellular carcinoma (HBV-HCC), therefore, we aimed to explore the changes in peripheral immunity in patients with HBV-HCC.MethodsIn this study, patients with HBV-HCC (n=26), patients with hepatitis B-related cirrhosis (HBV-LC) (n=31) and healthy volunteers (n=49) were included. The lymphocytes and their subpopulation phenotypes in peripheral blood were characterized. In addition, we explored the effect of viral replication on peripheral immunity in patients with HCC and analyzed the circulating immunophenotypic characteristics at different stages of HCC with flow cytometry.ResultsFirstly, our results showed that the percentages of total αβ T cells in the peripheral blood of HBV-HCC patients was significantly decreased compared to healthy subjects. Secondly, we found that naïve CD4+ T cells in HBV-HCC patients were significantly reduced, terminally differentiated CD8+ T cells, homing memory CD8+ T cells and Th2 cells were increased in peripheral circulation in HBV-HCC patients. Moreover, in the peripheral blood of HBV-HCC patients, expression of TIGIT on CD4+ T cells and PD-1 on the surface of Vδ 1 T cells was increased. In addition, we found that sustained viral replication resulted in up-regulation of TIM3 expression on CD4+ T cells, and TIM3+ γδ T cells increased in peripheral circulation in patients with advanced HBV-HCC.ConclusionOur study showed that circulating lymphocytes in HBV-HCC patients exhibited features of immune exhaustion, especially in HCC patients with persistent viral replication and in patients with intermediate and advanced HBV-HCC, including decreased frequency of T cells and elevated expression of inhibitory receptors including TIGIT and TIM3 on CD4+ T cells and γδ T cells. Meanwhile, our research suggests that the combination of CD3+ T cell and CD8+HLADR+CD38+ T cell may be a potential diagnostic indicator for HBV-HCC. These findings could help us to better understand the immune characteristics of HBV-HCC and explore the immune mechanisms and immunotherapy strategies for HBV-HCC.

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Section: Discussionmentioning

confidence: 99%

Peripheral immune characteristics of hepatitis B virus-related hepatocellular carcinoma

Sun

Lin

et al. 2023

Front. Immunol.

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“… 58 100 101 102 103 In the future, a unique application of scRNA-seq in combination with such GWAS analyses could delineate the precise cellular source of such disease-associated gene variants. 104 105 While these combined analyses are still being refined, they have previously clarified the cellular origins for genetic alterations of interest in ulcerative colitis 105 and could be applied to autoimmune liver diseases.…”

Section: Future Perspectivesmentioning

confidence: 99%

Unraveling the Complexity of Liver Disease One Cell at a Time

et al. 2022

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The human liver is a complex organ made up of multiple specialized cell types that carry out key physiological functions. An incomplete understanding of liver biology limits our ability to develop therapeutics to prevent chronic liver diseases, liver cancers, and death as a result of organ failure. Recently, single-cell modalities have expanded our understanding of the cellular phenotypic heterogeneity and intercellular cross-talk in liver health and disease. This review summarizes these findings and looks forward to highlighting new avenues for the application of single-cell genomics to unravel unknown pathogenic pathways and disease mechanisms for the development of new therapeutics targeting liver pathology. As these technologies mature, their integration into clinical data analysis will aid in patient stratification and in developing treatment plans for patients suffering from liver disease.

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Integrating single-cell RNA sequencing data to genome-wide association analysis data identifies significant cell types in influenza A virus infection and COVID-19

Zou

Sun

Wang

et al. 2023

Briefings in Functional Genomics

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With the global pandemic of COVID-19, the research on influenza virus has entered a new stage, but it is difficult to elucidate the pathogenesis of influenza disease. Genome-wide association studies (GWASs) have greatly shed light on the role of host genetic background in influenza pathogenesis and prognosis, whereas single-cell RNA sequencing (scRNA-seq) has enabled unprecedented resolution of cellular diversity and in vivo following influenza disease. Here, we performed a comprehensive analysis of influenza GWAS and scRNA-seq data to reveal cell types associated with influenza disease and provide clues to understanding pathogenesis. We downloaded two GWAS summary data, two scRNA-seq data on influenza disease. After defining cell types for each scRNA-seq data, we used RolyPoly and LDSC-cts to integrate GWAS and scRNA-seq. Furthermore, we analyzed scRNA-seq data from the peripheral blood mononuclear cells (PBMCs) of a healthy population to validate and compare our results. After processing the scRNA-seq data, we obtained approximately 70 000 cells and identified up to 13 cell types. For the European population analysis, we determined an association between neutrophils and influenza disease. For the East Asian population analysis, we identified an association between monocytes and influenza disease. In addition, we also identified monocytes as a significantly related cell type in a dataset of healthy human PBMCs. In this comprehensive analysis, we identified neutrophils and monocytes as influenza disease-associated cell types. More attention and validation should be given in future studies.

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Leveraging Single-Cell RNA-seq Data to Uncover the Association Between Cell Type and Chronic Liver Diseases

Cited by 4 publications

References 50 publications

Peripheral immune characteristics of hepatitis B virus-related hepatocellular carcinoma

Peripheral immune characteristics of hepatitis B virus-related hepatocellular carcinoma

Unraveling the Complexity of Liver Disease One Cell at a Time

Integrating single-cell RNA sequencing data to genome-wide association analysis data identifies significant cell types in influenza A virus infection and COVID-19

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