{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T14:29:29Z","timestamp":1792506569974,"version":"4.5.0"},"reference-count":31,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["YDZX2025015"],"award-info":[{"award-number":["YDZX2025015"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Hepatocellular carcinoma (HCC) exhibits pronounced cellular heterogeneity and dynamic state transitions during tumour progression, yet the emergence of tumour cell states along fate trajectories and their transcriptional regulation remain unclear. Here, we established an integrated framework linking cell fate dynamics with transcriptional regulatory networks using publicly available single\u2010cell RNA sequencing data. Malignant cells were identified by inferred copy number variation, followed by CellRank\u2010based fate inference and SCENIC\u2010based regulatory network reconstruction. We identified three terminal HCC cell states\u2014immune\u2010activated, metabolic, and proliferative hepatocytes\u2014forming a differentiation continuum from stem\u2010like to more mature phenotypes. Each state was governed by a distinct regulatory network with specific core regulators, including IRF3, PPARA, and JUN. Integration with TCGA\u2010LIHC bulk transcriptomic and clinical data revealed that a proliferative state\u2013derived transcriptional signature was associated with poorer overall survival. Together, our study provides a mechanistic framework linking tumour cell fate trajectories, regulatory heterogeneity and clinical outcomes in HCC.<\/jats:p>","DOI":"10.1111\/jcmm.71214","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T04:14:56Z","timestamp":1779768896000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Single\u2010Cell Characterization of Terminal States and State\u2010Specific Transcriptional Regulatory Networks in Hepatocellular Carcinoma"],"prefix":"10.1111","volume":"30","author":[{"given":"Biaolong","family":"Deng","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Science Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Science Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhao","family":"Lin","sequence":"additional","affiliation":[{"name":"College of Science Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lang","family":"Lu","sequence":"additional","affiliation":[{"name":"College of Science Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Science Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Science Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Science Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(25)01042\u20106"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000387"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.82177"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.240663.118"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2023.1158341"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576\u2010023\u201000618\u20105"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw550"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556\u2010022\u201000989\u20107"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592\u2010021\u201001346\u20106"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592\u2010024\u201002303\u20109"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201032283\u20103"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4463"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.10.045"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2021.12.162"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2021.100324"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2019.4689"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0301\u2010472x(01)00745\u20107"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14881"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn112150\u201020221124\u201001148"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.27852"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.16812"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2025.101160"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2015.03.004"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0177843"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2020.144437"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885\u2010024\u201012065\u20104"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2014.3668"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S509625"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.43640"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/5758601"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12010\u2010023\u201004443\u20108"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.71214","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jcmm.71214","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.71214","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T18:00:43Z","timestamp":1786384843000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.71214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":31,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1111\/jcmm.71214"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.71214","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"2026-03-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71214"}}