Expansion of macrophage and liver sinusoidal endothelial cell subpopulations during non-alcoholic steatohepatitis progression
Summary: Liver non-parenchymal cells (NPCs) play a critical role in the progression of non-alcoholic steatohepatitis (NASH). We aimed to explore the heterogeneity of NPCs and identify NASH-specific subpopulations contributing to NASH progression. Through single-cell RNA sequencing, we uncovered a pr...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223006491 |
| _version_ | 1797844995128950784 |
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| author | Zhenyang Shen Bo Shen Weiming Dai Cui Zhou Xin Luo Yuecheng Guo Junjun Wang Xianjun Xu Zhongshang Sun Xiaobo Cai Hui Dong Lungen Lu |
| author_facet | Zhenyang Shen Bo Shen Weiming Dai Cui Zhou Xin Luo Yuecheng Guo Junjun Wang Xianjun Xu Zhongshang Sun Xiaobo Cai Hui Dong Lungen Lu |
| author_sort | Zhenyang Shen |
| collection | DOAJ |
| description | Summary: Liver non-parenchymal cells (NPCs) play a critical role in the progression of non-alcoholic steatohepatitis (NASH). We aimed to explore the heterogeneity of NPCs and identify NASH-specific subpopulations contributing to NASH progression. Through single-cell RNA sequencing, we uncovered a proinflammatory subpopulation of Itgadhi/Fcrl5hi macrophages with potential function of modulating macrophage accumulation and promoting NASH development. We also identified subpopulations of Egr1hi and Ly6ahi liver sinusoidal endothelial cells (LSECs), which might participate in pathological angiogenesis and inflammation regulation. The Itgadhi/Fcrl5hi macrophages, Egr1hi LSECs, and Ly6ahi LSECs emerged in the early stage and expanded significantly along with pathological progression of liver injury during NASH. Cell-cell interactions between hepatic stellate cells (HSCs) and Itgadhi/Fcrl5hi macrophages, Egr1hi LSECs or Ly6ahi LSECs were enhanced in NASH liver. Our results revealed that expansion of Itgadhi/Fcrl5hi macrophages, Egr1hi LSECs or Ly6ahi LSECs was strongly associated with NASH severity, suggesting these subpopulations might be involved in NASH progression. |
| first_indexed | 2024-04-09T17:32:27Z |
| format | Article |
| id | doaj.art-62dd5b7522cf41feade3978f7114a5d2 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-09T17:32:27Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-62dd5b7522cf41feade3978f7114a5d22023-04-18T04:09:06ZengElsevieriScience2589-00422023-05-01265106572Expansion of macrophage and liver sinusoidal endothelial cell subpopulations during non-alcoholic steatohepatitis progressionZhenyang Shen0Bo Shen1Weiming Dai2Cui Zhou3Xin Luo4Yuecheng Guo5Junjun Wang6Xianjun Xu7Zhongshang Sun8Xiaobo Cai9Hui Dong10Lungen Lu11Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Gastroenterology, Shanghai General Hospital, Nanjing Medical University, Shanghai, ChinaDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding authorDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding authorDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding authorSummary: Liver non-parenchymal cells (NPCs) play a critical role in the progression of non-alcoholic steatohepatitis (NASH). We aimed to explore the heterogeneity of NPCs and identify NASH-specific subpopulations contributing to NASH progression. Through single-cell RNA sequencing, we uncovered a proinflammatory subpopulation of Itgadhi/Fcrl5hi macrophages with potential function of modulating macrophage accumulation and promoting NASH development. We also identified subpopulations of Egr1hi and Ly6ahi liver sinusoidal endothelial cells (LSECs), which might participate in pathological angiogenesis and inflammation regulation. The Itgadhi/Fcrl5hi macrophages, Egr1hi LSECs, and Ly6ahi LSECs emerged in the early stage and expanded significantly along with pathological progression of liver injury during NASH. Cell-cell interactions between hepatic stellate cells (HSCs) and Itgadhi/Fcrl5hi macrophages, Egr1hi LSECs or Ly6ahi LSECs were enhanced in NASH liver. Our results revealed that expansion of Itgadhi/Fcrl5hi macrophages, Egr1hi LSECs or Ly6ahi LSECs was strongly associated with NASH severity, suggesting these subpopulations might be involved in NASH progression.http://www.sciencedirect.com/science/article/pii/S2589004223006491ImmunologyCell biologyTranscriptomics |
| spellingShingle | Zhenyang Shen Bo Shen Weiming Dai Cui Zhou Xin Luo Yuecheng Guo Junjun Wang Xianjun Xu Zhongshang Sun Xiaobo Cai Hui Dong Lungen Lu Expansion of macrophage and liver sinusoidal endothelial cell subpopulations during non-alcoholic steatohepatitis progression iScience Immunology Cell biology Transcriptomics |
| title | Expansion of macrophage and liver sinusoidal endothelial cell subpopulations during non-alcoholic steatohepatitis progression |
| title_full | Expansion of macrophage and liver sinusoidal endothelial cell subpopulations during non-alcoholic steatohepatitis progression |
| title_fullStr | Expansion of macrophage and liver sinusoidal endothelial cell subpopulations during non-alcoholic steatohepatitis progression |
| title_full_unstemmed | Expansion of macrophage and liver sinusoidal endothelial cell subpopulations during non-alcoholic steatohepatitis progression |
| title_short | Expansion of macrophage and liver sinusoidal endothelial cell subpopulations during non-alcoholic steatohepatitis progression |
| title_sort | expansion of macrophage and liver sinusoidal endothelial cell subpopulations during non alcoholic steatohepatitis progression |
| topic | Immunology Cell biology Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223006491 |
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