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Natural killer (NK) cells can kill activated hepatic stellate cells (HSCs) against hepatic fibrosis. We used single-cell sequencing to screen hepatic NK cell subsets against schistosomiasis liver fibrosis. Hepatic NK cells were isolated from uninfected mice and mice infected for four and six weeks. The NK cells underwent single-cell sequencing. The markers\u2019 expression in the NK subsets was detected through Reverse Transcription\u2013Quantitative PCR (RT-qPCR). The proportion and granzyme B (Gzmb) expression of the total NK and Thy1+NK were detected. NK cells overexpressing Thy1 (Thy1-OE) were constructed, and functions were detected. The results revealed that the hepatic NK cells could be divided into mature, immature, regulatory-like, and memory-like NK cells and re-clustered into ten subsets. C3 (Cx3cr1+NK) and C4 (Thy1+NK) increased at week four post-infection, and other subsets decreased continuously. The successfully constructed Thy1-OE NK cells had significantly higher effector molecules and induced greater HSC apoptosis than the control NK cells. It revealed a pattern of hepatic NK cells in a mouse model of schistosomiasis. The Thy1+NK cells could be used as target cells against hepatic fibrosis.<\/jats:p>","DOI":"10.3390\/ijms26073211","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T03:25:02Z","timestamp":1743391502000},"page":"3211","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Single-Cell Sequencing Reveals the Heterogeneity of Hepatic Natural Killer Cells and Identifies the Cytotoxic Natural Killer Subset in Schistosomiasis Mice"],"prefix":"10.3390","volume":"26","author":[{"given":"Fangfang","family":"Xu","sequence":"first","affiliation":[{"name":"National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases, Ministry of Science and Technology, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Gao","sequence":"additional","affiliation":[{"name":"National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases, Ministry of Science and Technology, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teng","family":"Li","sequence":"additional","affiliation":[{"name":"National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases, Ministry of Science and Technology, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Jiang","sequence":"additional","affiliation":[{"name":"National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases, Ministry of Science and Technology, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoying","family":"Wu","sequence":"additional","affiliation":[{"name":"National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases, Ministry of Science and Technology, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihao","family":"Yu","sequence":"additional","affiliation":[{"name":"National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Parasite and Vector 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5439-8822","authenticated-orcid":false,"given":"Yuan","family":"Hu","sequence":"additional","affiliation":[{"name":"National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases, Ministry of Science and Technology, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1974-0047","authenticated-orcid":false,"given":"Jianping","family":"Cao","sequence":"additional","affiliation":[{"name":"National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases, Ministry of Science and Technology, Shanghai 200025, China"},{"name":"School of Global Health, Chinese Center for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1056\/NEJMoa1812165","article-title":"Schistosomiasis- assessing progress toward the 2020 and 2025 global goals","volume":"381","author":"Deol","year":"2019","journal-title":"N. 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