Xi XL, Yang YD, Liu HL, Jiang J, Wu B. Chromatin accessibility module identified by single-cell sequencing underlies the diagnosis and prognosis of hepatocellular carcinoma. World J Hepatol 2025; 17(6): 107329 [PMID: 40606924 DOI: 10.4254/wjh.v17.i6.107329]
Corresponding Author of This Article
Bin Wu, MD, PhD, Professor, Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China. wubin6@mail.sysu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
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Basic Study
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Jun 27, 2025 (publication date) through Oct 31, 2025
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Publication Name
World Journal of Hepatology
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1948-5182
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Xi XL, Yang YD, Liu HL, Jiang J, Wu B. Chromatin accessibility module identified by single-cell sequencing underlies the diagnosis and prognosis of hepatocellular carcinoma. World J Hepatol 2025; 17(6): 107329 [PMID: 40606924 DOI: 10.4254/wjh.v17.i6.107329]
World J Hepatol. Jun 27, 2025; 17(6): 107329 Published online Jun 27, 2025. doi: 10.4254/wjh.v17.i6.107329
Chromatin accessibility module identified by single-cell sequencing underlies the diagnosis and prognosis of hepatocellular carcinoma
Xiao-Li Xi, Yi-Dong Yang, Hui-Ling Liu, Jie Jiang, Bin Wu
Xiao-Li Xi, Yi-Dong Yang, Hui-Ling Liu, Jie Jiang, Bin Wu, Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China
Co-first authors: Xiao-Li Xi and Yi-Dong Yang.
Author contributions: Xi XL and Yang YD analyzed the data and wrote the manuscript, they contributed equally to this article, they are the co-first authors of this manuscript; Xi XL, Liu HL, and Jiang J performed the research; Yang YD contributed new reagents and analytic tools; Wu B designed the research study; and all authors have read and approved the final manuscript.
Supported by the Science and Technology Planning Project of Guangzhou, No. 2024A03J0102; the Natural Science Foundation of Guangdong Province for Distinguished Young Scholar, No. 2022B1515020024; National Natural Science Foundation of China, No. 82070574; and the Key Research and Development Program of Guangzhou, No. 2023B03J1298.
Institutional review board statement: This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-Sen University, approval No. [2019]02-248-01.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets obtained and explored in this study are available in the TCGA (https://portal.gdc.cancer.gov/) and GEO dataset. The original contributions presented in the study are included in the article. Further inquiries could be directed to the corresponding author.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Bin Wu, MD, PhD, Professor, Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China. wubin6@mail.sysu.edu.cn
Received: March 21, 2025 Revised: April 24, 2025 Accepted: May 29, 2025 Published online: June 27, 2025 Processing time: 98 Days and 1.2 Hours
Core Tip
Core Tip: This study unveils multilayered chromatin accessibility dynamics in hepatocellular carcinoma. Single-cell multiomics analysis discovered malignant hepatocytes adopting increased numbers of accessible peaks and larger physical regions despite reduced peak intensity, while tumor-stroma intercellular chromatin coaccessibility maintains tumor ecological symbiosis. Functional validation identified DGAT1 as an epigenetic vulnerability: Pharmacological histone 3 lysine 27 acetylation inhibition and relating decreased chromatin accessibility suppressed DGAT1 expression, and DGAT1 knockdown further blocked tumor growth. Our findings redefine hepatocellular carcinoma progression as a chromatin-adaptive disorder governed by tumor-intrinsic epigenetic prioritization and microenvironmental crosstalk, proposing simultaneous targeting of chromatin hub genes and compensatory pathways as precision strategies.
