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Hepatitis B virus compartmentalization and single-cell differentiation in hepatocellular carcinoma.
Life Science Alliance ( IF 4.4 ) Pub Date : 2021-07-21 , DOI: 10.26508/lsa.202101036
Frank Jühling 1 , Antonio Saviano 1, 2 , Clara Ponsolles 1 , Laura Heydmann 1 , Emilie Crouchet 1 , Sarah C Durand 1 , Houssein El Saghire 1 , Emanuele Felli 1, 2 , Véronique Lindner 3 , Patrick Pessaux 1, 2 , Nathalie Pochet 4, 5 , Catherine Schuster 1, 2 , Eloi R Verrier 6 , Thomas F Baumert 2, 6, 7
Affiliation  

Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC) world-wide. The molecular mechanisms of viral hepatocarcinogenesis are still partially understood. Here, we applied two complementary single-cell RNA-sequencing protocols to investigate HBV-HCC host cell interactions at the single cell level of patient-derived HCC. Computational analyses revealed a marked HCC heterogeneity with a robust and significant correlation between HBV reads and cancer cell differentiation. Viral reads significantly correlated with the expression of HBV-dependency factors such as HLF in different tumor compartments. Analyses of virus-induced host responses identified previously undiscovered pathways mediating viral carcinogenesis, such as E2F- and MYC targets as well as adipogenesis. Mapping of fused HBV-host cell transcripts allowed the characterization of integration sites in individual cancer cells. Collectively, single-cell RNA-Seq unravels heterogeneity and compartmentalization of both, virus and cancer identifying new candidate pathways for viral hepatocarcinogenesis. The perturbation of pro-carcinogenic gene expression even at low HBV levels highlights the need of HBV cure to eliminate HCC risk.

中文翻译:

乙型肝炎病毒在肝细胞癌中的区室化和单细胞分化。

慢性乙型肝炎病毒 (HBV) 感染是全球肝细胞癌 (HCC) 的主要原因。病毒性肝癌发生的分子机制仍部分了解。在这里,我们应用了两种互补的单细胞 RNA 测序方案来研究 HBV-HCC 宿主细胞在患者来源的 HCC 的单细胞水平上的相互作用。计算分析揭示了显着的 HCC 异质性,在 HBV 读数和癌细胞分化之间具有强大且显着的相关性。病毒读数与 HBV 依赖因子(如HLF )的表达显着相关在不同的肿瘤区室。对病毒诱导的宿主反应的分析确定了以前未发现的介导病毒致癌作用的途径,例如 E2F 和 MYC 靶标以及脂肪生成。融合的 HBV 宿主细胞转录物的映射允许对单个癌细胞中的整合位点进行表征。总的来说,单细胞 RNA-Seq 揭示了病毒和癌症的异质性和划分,确定了病毒性肝癌发生的新候选途径。即使在低 HBV 水平下,促癌基因表达也会受到干扰,这突出了需要治愈 HBV 以消除 HCC 风险。
更新日期:2021-07-21
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