{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:04:47Z","timestamp":1789538687477,"version":"build-2803163510"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    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\n                    <jats:italic>FDR<\/jats:italic>\n                    -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 (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a00.00368). 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.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1923630","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:31:50Z","timestamp":1789536710000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative transcriptomic and single-cell analysis reveals a convergent cholangiocyte-associated host inflammatory program in biliary atresia and SARS-CoV-2-associated hepatobiliary injury"],"prefix":"10.3389","volume":"17","author":[{"given":"Yujuan","family":"Wa","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, School of Basic Medical Sciences, Harbin Medical University","place":["Harbin, China"]},{"name":"Key Laboratory of Preservation of Human Genetic 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rouchen","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Harbin Medical University","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, School of Basic Medical Sciences, Harbin Medical University","place":["Harbin, China"]},{"name":"Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianglei","family":"Guang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, School of Basic Medical Sciences, Harbin Medical University","place":["Harbin, China"]},{"name":"Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, School of Basic Medical Sciences, Harbin Medical University","place":["Harbin, China"]},{"name":"Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, School of Basic Medical Sciences, Harbin Medical University","place":["Harbin, China"]},{"name":"Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, School of Basic Medical Sciences, Harbin Medical University","place":["Harbin, China"]},{"name":"Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingbo","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, The Sixth Affiliated Hospital of Harbin Medical University","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University","place":["Harbin, 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