2026-10-12T11:26:43Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33828589 2026-09-16T05:30:09Z category_696 portal_316 item_type_3 month_year_09_2026

Supplementary file 1_Integrative transcriptomic and single-cell analysis reveals a convergent cholangiocyte-associated host inflammatory program in biliary atresia and SARS-CoV-2-associated hepatobiliary injury.docx Yujuan Wa (24961054) Rong Guan (729808) Zhanwei Du (4867891) Rouchen Lin (24961057) Shiyu Cui (15831413) Jianglei Guang (24961060) Lidan Xu (291212) Wei Ji (15028) Qian Yang (300330) Qingbo Cui (10956834) Hao Wang (39217) Wenjing Sun (228791) Genetic Immunology biliary atresia cholangiocyte host inflammatory response integrative transcriptomics pediatric cholangiopathy perinatal infection SARS-CoV-2 single-cell transcriptomics <p>SARS-CoV-2-associated hepatobiliary injury and biliary atresia (BA) differ markedly in etiology and biological context, but both involve injury to the biliary epithelial compartment. Here, we performed integrative transcriptomic and single-cell analyses to investigate whether these distinct hepatobiliary injury contexts converge on a shared cholangiocyte-associated inflammatory host-response program. Bulk transcriptomic datasets from SARS-CoV-2-infected human liver organoids and BA liver tissues were integrated to identify shared transcriptional alterations, followed by functional enrichment, protein-protein interaction, regulatory network, drug-gene interaction, and molecular docking analyses. Single-nucleus and single-cell datasets were used to determine the cellular localization of the shared program, and key findings were further assessed in BA liver tissues and cultured human cholangiocytes exposed to poly(I:C). We identified an expanded exploratory set of 164 shared genes and a stringent FDR-adjusted core of 52 genes. Both sets consistently implicated antiviral defense, type I and type II interferon signaling, double-stranded RNA responses, and cytokine and chemokine signaling. STAT1, ISG15, and CXCL10 were retained in the stringent core and remained central components of the interaction network. In COVID-19 liver single-nucleus data, donor-level analysis showed preferential localization of the shared signature to cholangiocytes, whose mean scores were significantly higher than those of all other hepatic cells combined (P = 0.00368). A similar pattern was observed descriptively in our BA single-nucleus dataset and further supported by an independent BA single-cell cohort. Tissue immunofluorescence spatially associated pSTAT1, total STAT1, and ISG15 signals with KRT19-positive ductular structures, whereas CXCL10 was predominantly periductal. Poly(I:C) stimulation induced representative components of the program in cultured cholangiocytes. Computational analyses retained mefloquine among the top-ranked exploratory candidates. Collectively, these findings support a convergent cholangiocyte-associated interferon/inflammatory host-response program in BA and SARS-CoV-2-associated hepatobiliary injury. They indicate molecular association rather than a common etiology or causal relationship and provide testable hypotheses for further investigation of biliary epithelial inflammatory responses.</p> 2026-09-16T05:30:09Z Dataset Dataset 10.3389/fimmu.2026.1923630.s001 https://figshare.com/articles/dataset/Supplementary_file_1_Integrative_transcriptomic_and_single-cell_analysis_reveals_a_convergent_cholangiocyte-associated_host_inflammatory_program_in_biliary_atresia_and_SARS-CoV-2-associated_hepatobiliary_injury_docx/33828589 CC BY 4.0