{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T13:59:39Z","timestamp":1788184779288,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072650"],"award-info":[{"award-number":["82072650"]}],"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":["32100730"],"award-info":[{"award-number":["32100730"]}],"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":["81802844"],"award-info":[{"award-number":["81802844"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100022963","name":"Key Research and Development Program of Zhejiang Province","doi-asserted-by":"publisher","award":["2021C03121"],"award-info":[{"award-number":["2021C03121"]}],"id":[{"id":"10.13039\/100022963","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>The relationship between chronic liver disease and liver cancer remains poorly understood, and treatment options for advanced liver disease remain limited. This study aims to elucidate the dynamic evolution of cellular and molecular alterations from normal liver to diseased liver.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Single\u2010cell RNA sequencing was performed to profile the dynamic cellular variations from normal liver to diseased liver. Bioinformatics analyses were employed to assess tumour heterogeneity and the evolution of tumour microenvironment. Molecular biology validations were performed to investigate the findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Through single\u2010cell RNA sequencing, we constructed a human liver landscape consisting of more than 130 000 single cells, from normal, cirrhotic tissue, primary liver cancer and paired adjacent tissues. We profiled both inter\u2010 and intra\u2010tumour heterogeneity of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. A dual role of the pro\u2010fibrosis and pro\u2010carcinogenesis FABP5\n                      <jats:sup>high<\/jats:sup>\n                      macrophage subset was shown to be conserved throughout the progression of liver fibrosis and carcinogenesis; markers, spatial localization, origin, and functional pathways associated with FABP5\n                      <jats:sup>high<\/jats:sup>\n                      macrophages were identified through in\u00a0vitro and in\u00a0vivo validation. Metabolic reprogramming of these conserved FABP5\n                      <jats:sup>high<\/jats:sup>\n                      macrophages is implicated in the formation of cirrhotic and cancerous niches. Additionally, we also identified a subset of RGCC+COL4A1+ endothelial cells enriched in HCC tissues, which might experience endothelial\u2010mesenchymal transition and orchestrate the proliferation and invasion of cancer cells via angiogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings provide insights into the evolution from chronic liver disease to liver cancer. These insights will contribute to the development of novel cell subset\u2010based therapeutics based on immunotherapy and targeted therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70262","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T13:25:29Z","timestamp":1756387529000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Conserved\n                    <scp>\n                      FABP5\n                      <sup>high<\/sup>\n                    <\/scp>\n                    Macrophage Subset Promotes Fibrosis and Carcinogenesis in Advanced Liver Disease"],"prefix":"10.1111","volume":"45","author":[{"given":"Wenhao","family":"Ge","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"},{"name":"Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifeng","family":"Ma","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplantation Center of the First Affiliated Hospital, and Center for Stem Cell and Regenerative Medicine Zhejiang University School of Medicine  Hangzhou China"},{"name":"Liangzhu Laboratory Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"},{"name":"Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weigao","family":"E","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplantation Center of the First Affiliated Hospital, and Center for Stem Cell and Regenerative Medicine Zhejiang University School of Medicine  Hangzhou China"},{"name":"Liangzhu Laboratory Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujing","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, Shanghai Institute of Immunology Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bijun","family":"Cui","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Wang","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplantation Center of the First Affiliated Hospital, and Center for Stem Cell and Regenerative Medicine Zhejiang University School of Medicine  Hangzhou China"},{"name":"Liangzhu Laboratory Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutian","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"},{"name":"Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplantation Center of the First Affiliated Hospital, and Center for Stem Cell and Regenerative Medicine Zhejiang University School of Medicine  Hangzhou China"},{"name":"Liangzhu Laboratory Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"},{"name":"Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengxuan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery and Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China) the Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingsheng","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongkai","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"},{"name":"Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province  Hangzhou China"},{"name":"Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province  Hangzhou China"},{"name":"National Innovation Center for Fundamental Research on Cancer Medicine  Hangzhou China"},{"name":"Cancer Center Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Han","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplantation Center of the First Affiliated Hospital, and Center for Stem Cell and Regenerative Medicine Zhejiang University School of Medicine  Hangzhou China"},{"name":"Liangzhu Laboratory Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoji","family":"Guo","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplantation Center of the First Affiliated Hospital, and Center for Stem Cell and Regenerative Medicine Zhejiang University School of Medicine  Hangzhou China"},{"name":"Liangzhu Laboratory Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9432-2649","authenticated-orcid":false,"given":"Weilin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"},{"name":"Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province  Hangzhou China"},{"name":"Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province  Hangzhou China"},{"name":"National Innovation Center for Fundamental Research on Cancer Medicine  Hangzhou China"},{"name":"Cancer Center Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21708"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.21147\/j.issn.1000-9604.2018.06.01"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02728-8"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2157-4"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.035"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.10.003"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-020-0241-6"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2016.10.006"},{"issue":"118","key":"e_1_2_13_10_1","first-page":"489","article-title":"The Immunosuppression Role of Alpha\u2010Fetoprotein in Human Hepatocellular Carcinoma","volume":"21","author":"Meng W.","year":"2016","journal-title":"Discovery Medicine"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-021-01091-3"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30519"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab418"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI66024"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14256-1"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00646-4"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03651-8"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1631-3"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0044-z"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgab025"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2019-000501"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.126453"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-1285"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.07.009"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI161070"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1613"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2023.04.007"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.01.010"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.040"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32598-8"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.03.048"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-032620-104801"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.02.004"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00496-y"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.038"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI143690"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.00808"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.05.015"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.70262","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T14:06:25Z","timestamp":1764597985000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.70262"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,28]]},"references-count":37,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1111\/liv.70262"],"URL":"https:\/\/doi.org\/10.1111\/liv.70262","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,28]]},"assertion":[{"value":"2024-11-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70262"}}