{"doi":"10.26508/lsa.202101036","title":"Hepatitis B virus compartmentalization and single-cell differentiation in hepatocellular carcinoma","abstract":"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.","journal":"Life Science Alliance","year":2021,"id":194078,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":50894,"name":"Antonio Saviano","orcid":"0000-0001-7585-472X","position":1,"is_corresponding":false},{"id":50892,"name":"Clara Ponsolles","orcid":"0009-0000-6711-4238","position":2,"is_corresponding":false},{"id":50893,"name":"Laura Heydmann","orcid":"0000-0002-2273-2267","position":3,"is_corresponding":false},{"id":50936,"name":"Émilie Crouchet","orcid":null,"position":4,"is_corresponding":false},{"id":763881,"name":"Sarah Durand","orcid":null,"position":5,"is_corresponding":false},{"id":286957,"name":"Houssein El Saghire","orcid":null,"position":6,"is_corresponding":false},{"id":50928,"name":"Emanuele Felli","orcid":"0000-0002-6510-1457","position":7,"is_corresponding":false},{"id":763268,"name":"Véronique Lindner","orcid":"0000-0001-5140-5321","position":8,"is_corresponding":false},{"id":50929,"name":"Patrick Pessaux","orcid":"0000-0001-5635-7437","position":9,"is_corresponding":false},{"id":3256,"name":"Nathalie Pochet","orcid":"0000-0003-1820-5656","position":10,"is_corresponding":false},{"id":50931,"name":"Catherine Schuster","orcid":"0000-0001-7281-4511","position":11,"is_corresponding":false},{"id":50898,"name":"Eloi R. Verrier","orcid":"0000-0002-9022-5611","position":12,"is_corresponding":false},{"id":50935,"name":"Thomas F. Baumert","orcid":"0000-0002-8864-2168","position":13,"is_corresponding":false},{"id":763880,"name":"Frank Juehling","orcid":null,"position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-18T23:49:55.282992Z","pmid":"34290079","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}