{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:37:45Z","timestamp":1792013865472,"version":"4.4.0"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006407","name":"Natural Science Foundation of Henan Province","doi-asserted-by":"publisher","award":["242300420070"],"award-info":[{"award-number":["242300420070"]}],"id":[{"id":"10.13039\/501100006407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81988101"],"award-info":[{"award-number":["81988101"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073411"],"award-info":[{"award-number":["82073411"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Alcohol\u2010related liver disease (ALD) is a common chronic liver disease caused by long\u2010term excessive alcohol consumption and responsible for more than half of all liver\u2010related deaths worldwide. The molecular mechanisms associated with ALD were not fully understood. In this study, we performed single\u2010cell RNA sequencing on liver tissues obtained from ALD patients and healthy liver donors. We identified an ALB<jats:sup>+<\/jats:sup>KRT7<jats:sup>+<\/jats:sup> epithelial population that expressed both hepatocyte and biliary markers significantly expanded in ALD livers. The ALB<jats:sup>+<\/jats:sup>KRT7<jats:sup>+<\/jats:sup> epithelial cells were demonstrated to have stem cell properties and malignant transformation potentials. Moreover, ALB<jats:sup>+<\/jats:sup>KRT7<jats:sup>+<\/jats:sup> epithelium\u2010derived ALD organoids promote the tumour growth by activating Wnt\/\u03b2\u2010catenin signalling of liver cancer cells. Most importantly, blocking the Wnt protein secretion or knockdown the Wnt receptor suppressed the tumour promoting effect of ALD organoids. Our study provides important insights that Wnt signalling can be targeted in patients with advanced alcohol\u2010related cirrhosis to prevent malignant transformation. In addition, our results also uncovered the important alterations of nonparenchymal cells, especially macrophages and T\/NK populations that responsible for active inflammation responses in alcohol\u2010related hepatitis and immunosuppressive microenvironment in advanced cirrhosis livers, which likely facilitated the malignant progression of ALD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>This study provides single\u2010cell landscape of human liver samples across different ALD stages.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The ALB<jats:sup>+<\/jats:sup> KRT7<jats:sup>+<\/jats:sup> epithelium were enriched in ALD patients, and the function of this epithelial population varied significantly across ALD stages.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>ALB<jats:sup>+<\/jats:sup>KRT7<jats:sup>+<\/jats:sup> epithelium from advanced alcohol\u2010related cirrhosis had malignant transformation potential and tumour promotion activity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The comprehensive changes of parenchymal and nonparenchymal cells in the ALD livers lay a hidden danger for the further malignant progression.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.70198","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T01:37:43Z","timestamp":1737423463000},"source":"Crossref","is-referenced-by-count":9,"title":["Single\u2010cell landscape of the intrahepatic ecosystem in alcohol\u2010related liver disease"],"prefix":"10.1002","volume":"15","author":[{"given":"Xiaofang","family":"Zhao","sequence":"first","affiliation":[{"name":"Translational Medicine Center The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan China"},{"name":"International Cooperation Laboratory on Signal Transduction, National Center for Liver Cancer, Ministry of Education Key Laboratory on Signaling Regulation and Targeting Therapy of Liver Cancer, Shanghai Key Laboratory of Hepatobiliary Tumor Biology Eastern Hepatobiliary Surgery Hospital, Second Military Medical University\/NAVAL Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Translational Medicine Center The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Wei","sequence":"additional","affiliation":[{"name":"Translational Medicine Center The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan 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