Single-cell atlas of hepatitis C virus inoculated tree shrew liver reveals immune activation, metabolic reprogramming, and persistent inflammation
文献类型：期刊论文
| 作者 | Yu, Dandan4,5,6,7; Kang, Wei-Bo4,5,7; Ma, Yu-Hua6; Lv, Long-Bao6; Zhang, Shihua2; Tang, Lei1; Liu, Sheng1; Zhong, Jin3; Yao, Yong-Gang4,5,6,7 |
| 刊名 | EBIOMEDICINE
 |
| 出版日期 | 2026 |
| 卷号 | 123页码:23 |
| 关键词 | HCV Chinese tree shrew Single-cell RNA sequencing Hepatocytes Erythroblasts Neutrophils |
| ISSN号 | 2352-3964 |
| DOI | 10.1016/j.ebiom.2025.106080 |
| 通讯作者 | Zhong, Jin(yaoyg@mail.kiz.ac.cn) ; Yao, Yong-Gang(jzhong@ips.ac.cn) |
| 英文摘要 | Background Hepatitis C virus (HCV) remains a major global health challenge, largely due to the absence of robust animal models that recapitulate this disease, hindering mechanistic studies and vaccine development. This study employed tree shrews to determine the molecular profiles of distinct liver cell populations following HCV infection. Methods Tree shrews received intrahepatic injections of the HCV JFH1 strain and were analysed at two timepoints: 1 week post-inoculation (acute) and 111 weeks post-inoculation (long-term). Viral load was assessed up to 30 weeks. Liver pathology was assessed via haematoxylin and eosin (H&E) staining. Single-cell transcriptomic profiling was performed on liver tissues, while tree shrew primary hepatocytes and ITH6 hepatic cells, as well as human Huh7 cells, were used to characterise cellular changes following HCV infection. Findings Sixteen major cell types were identified in 157,298 liver cells across HCV-inoculated and control tree shrews. Acute inoculation triggered widespread induction of interferon-stimulated genes (ISGs) across all cell types, including the periportal ISG high hepatocyte subcluster, and concurrent reduction in metabolic gene expression in hepatocytes in vivo. Impaired glucose metabolism, as confirmed in HCV-exposed ITH6 cells, likely contributed to this metabolic shift. Erythroblasts were exclusively detected during acute inoculation and exhibited enhanced intercellular communication signatures. Among neutrophils, three distinct subclusters were identified, one of which displayed elevated expression of neutrophil extracellular trap (NET) markers and enhanced NET formation in inoculated livers. Interpretation This study provides a comprehensive single-cell transcriptomic landscape of HCV-inoculated tree shrew livers. These findings underscore the use of the tree shrew model for advancing mechanistic understanding of HCV pathogenesis, as well as its relevance for therapeutic and vaccine development. Copyright (c) 2025 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| WOS关键词 | TUPAIA-BELANGERI ; INTERFERON-LAMBDA ; INNATE IMMUNITY ; UP-REGULATION ; INFECTION ; RNA ; MODEL ; GLUCOSE ; IDENTIFICATION ; TRANSMISSION |
| 资助项目 | National Natural Science Foundation of China[U1902215] ; National Natural Science Foundation of China[U25A20646] ; National Key Research and Development Plan Program[2022YFF0710900] ; Key Project of the CAS Light of West China Program[xbzg-zdsys-202302] ; Yunnan Province[202305AH340006] ; Yunnan Province[202001AS070023] |
| WOS研究方向 | General & Internal Medicine ; Research & Experimental Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:001645969100001 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/322453]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zhong, Jin; Yao, Yong-Gang |
| 作者单位 | 1.Sun Yat sen Univ, Guangdong Prov Key Lab Ophthalmol & Visual Sci, Guangdong Prov Key Lab Brain Funct & Dis, State Key Lab Ophthalmol,Zhongshan Ophthalm Ctr, Guangzhou 510623, Peoples R China 2.Chinese Acad Sci, Acad Math & Syst Sci, State Key Lab Math Sci, Beijing 100190, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Immun & Infect, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China 4.Chinese Acad Sci, State Key Lab Genet Evolut & Anim Models, Key Lab Anim Models & Human Dis Mech Yunnan Prov, Kunming Inst Zool,Yunnan Engn Ctr Brain Dis Models, Kunming 650201, Yunnan, Peoples R China 5.Chinese Acad Sci, Kunming Inst Zool, KIZ CUHK Joint Lab Bioresources & Mol Res Common D, Kunming 650201, Yunnan, Peoples R China 6.Chinese Acad Sci, Kunming Inst Zool, Natl Resource Ctr Nonhuman Primates, Natl Res Facil Phenotyp & Genet Anal Model Anim Pr, Kunming 650107, Yunnan, Peoples R China 7.Univ Chinese Acad Sci, Kunming Coll Life Sci, Kunming 650204, Yunnan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yu, Dandan,Kang, Wei-Bo,Ma, Yu-Hua,et al. Single-cell atlas of hepatitis C virus inoculated tree shrew liver reveals immune activation, metabolic reprogramming, and persistent inflammation[J]. EBIOMEDICINE,2026,123:23. |
| APA | Yu, Dandan.,Kang, Wei-Bo.,Ma, Yu-Hua.,Lv, Long-Bao.,Zhang, Shihua.,...&Yao, Yong-Gang.(2026).Single-cell atlas of hepatitis C virus inoculated tree shrew liver reveals immune activation, metabolic reprogramming, and persistent inflammation.EBIOMEDICINE,123,23. |
| MLA | Yu, Dandan,et al."Single-cell atlas of hepatitis C virus inoculated tree shrew liver reveals immune activation, metabolic reprogramming, and persistent inflammation".EBIOMEDICINE 123(2026):23. |
入库方式： OAI收割
来源：上海药物研究所
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