Lingdu Meng, Min Du, Haodong Li, Fanyang Kong, Jiajian Yang, Rui Dong, Shan Zheng, Gong Chen, Zhen Shen, Junfeng Wang
{"title":"单细胞转录揭示了胆道闭锁中肝细胞到胆管细胞的重编程和胆道基因谱。","authors":"Lingdu Meng, Min Du, Haodong Li, Fanyang Kong, Jiajian Yang, Rui Dong, Shan Zheng, Gong Chen, Zhen Shen, Junfeng Wang","doi":"10.1097/HC9.0000000000000710","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Ductular reaction (DR), characterized by the expansion of biliary epithelial cells in the portal area, is a typical hepatic pathology for biliary atresia (BA). The cellular source and function of DR remain poorly understood. Herein, we performed single-cell RNA sequencing (scRNA-seq) in BA to resolve the complexity of DR in BA.</p><p><strong>Methods: </strong>A total of 4 BA and 3 normal control livers underwent scRNA-seq. The epithelial cells were extracted from all cells for further analysis. The cell types, functions, and differentiational trajectory of epithelial cells were determined. The biliary markers and transcription factors (TFs) were identified by combing public bulk and scRNA-seq data and validated by immunohistochemistry.</p><p><strong>Results: </strong>ScRNA-seq identified the existence of biliary reprogramming in BA, and the reprogrammed cells expressed both hepatocyte and cholangiocyte markers. When compared with hepatocytes, genes of epithelial-mesenchymal transition, fibrosis, inflammation, and RNA metabolism were enriched in cholangiocytes and upregulated in BA. Pseudotime analysis depicted a differentiation trajectory from hepatocytes across reprogrammed cells to cholangiocytes in BA. Matrix metalloproteinase 7 (MMP7), VTCN1, and LAMC2 were identified as the biliary markers, and KLF5 and HNF1B were determined as the biliary TFs in BA. All the biliary markers and TFs were upregulated in BA when compared with controls.</p><p><strong>Conclusions: </strong>Dissecting the cellular source and function of cholangiocytes is essential to understand the pathological role of DR in BA. The identified specific biliary markers and TFs provide important insights into its potential diagnosis and mechanism exploration for BA in the future.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 5","pages":""},"PeriodicalIF":5.6000,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055120/pdf/","citationCount":"0","resultStr":"{\"title\":\"Single-cell transcription reveals hepatocyte-to-cholangiocyte reprogramming and biliary gene profile in biliary atresia.\",\"authors\":\"Lingdu Meng, Min Du, Haodong Li, Fanyang Kong, Jiajian Yang, Rui Dong, Shan Zheng, Gong Chen, Zhen Shen, Junfeng Wang\",\"doi\":\"10.1097/HC9.0000000000000710\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Ductular reaction (DR), characterized by the expansion of biliary epithelial cells in the portal area, is a typical hepatic pathology for biliary atresia (BA). The cellular source and function of DR remain poorly understood. Herein, we performed single-cell RNA sequencing (scRNA-seq) in BA to resolve the complexity of DR in BA.</p><p><strong>Methods: </strong>A total of 4 BA and 3 normal control livers underwent scRNA-seq. The epithelial cells were extracted from all cells for further analysis. The cell types, functions, and differentiational trajectory of epithelial cells were determined. The biliary markers and transcription factors (TFs) were identified by combing public bulk and scRNA-seq data and validated by immunohistochemistry.</p><p><strong>Results: </strong>ScRNA-seq identified the existence of biliary reprogramming in BA, and the reprogrammed cells expressed both hepatocyte and cholangiocyte markers. When compared with hepatocytes, genes of epithelial-mesenchymal transition, fibrosis, inflammation, and RNA metabolism were enriched in cholangiocytes and upregulated in BA. Pseudotime analysis depicted a differentiation trajectory from hepatocytes across reprogrammed cells to cholangiocytes in BA. Matrix metalloproteinase 7 (MMP7), VTCN1, and LAMC2 were identified as the biliary markers, and KLF5 and HNF1B were determined as the biliary TFs in BA. All the biliary markers and TFs were upregulated in BA when compared with controls.</p><p><strong>Conclusions: </strong>Dissecting the cellular source and function of cholangiocytes is essential to understand the pathological role of DR in BA. The identified specific biliary markers and TFs provide important insights into its potential diagnosis and mechanism exploration for BA in the future.</p>\",\"PeriodicalId\":12978,\"journal\":{\"name\":\"Hepatology Communications\",\"volume\":\"9 5\",\"pages\":\"\"},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2025-05-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055120/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hepatology Communications\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/HC9.0000000000000710\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/5/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hepatology Communications","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/HC9.0000000000000710","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Single-cell transcription reveals hepatocyte-to-cholangiocyte reprogramming and biliary gene profile in biliary atresia.
Background: Ductular reaction (DR), characterized by the expansion of biliary epithelial cells in the portal area, is a typical hepatic pathology for biliary atresia (BA). The cellular source and function of DR remain poorly understood. Herein, we performed single-cell RNA sequencing (scRNA-seq) in BA to resolve the complexity of DR in BA.
Methods: A total of 4 BA and 3 normal control livers underwent scRNA-seq. The epithelial cells were extracted from all cells for further analysis. The cell types, functions, and differentiational trajectory of epithelial cells were determined. The biliary markers and transcription factors (TFs) were identified by combing public bulk and scRNA-seq data and validated by immunohistochemistry.
Results: ScRNA-seq identified the existence of biliary reprogramming in BA, and the reprogrammed cells expressed both hepatocyte and cholangiocyte markers. When compared with hepatocytes, genes of epithelial-mesenchymal transition, fibrosis, inflammation, and RNA metabolism were enriched in cholangiocytes and upregulated in BA. Pseudotime analysis depicted a differentiation trajectory from hepatocytes across reprogrammed cells to cholangiocytes in BA. Matrix metalloproteinase 7 (MMP7), VTCN1, and LAMC2 were identified as the biliary markers, and KLF5 and HNF1B were determined as the biliary TFs in BA. All the biliary markers and TFs were upregulated in BA when compared with controls.
Conclusions: Dissecting the cellular source and function of cholangiocytes is essential to understand the pathological role of DR in BA. The identified specific biliary markers and TFs provide important insights into its potential diagnosis and mechanism exploration for BA in the future.
期刊介绍:
Hepatology Communications is a peer-reviewed, online-only, open access journal for fast dissemination of high quality basic, translational, and clinical research in hepatology. Hepatology Communications maintains high standard and rigorous peer review. Because of its open access nature, authors retain the copyright to their works, all articles are immediately available and free to read and share, and it is fully compliant with funder and institutional mandates. The journal is committed to fast publication and author satisfaction.