Single-Cell RNA Sequencing Reveals Macrophage Dynamics During MASH in <i>Leptin</i>-Deficient Rats
Macrophages play important roles in metabolic dysfunction-associated steatohepatitis (MASH), an advanced and inflammatory stage of metabolic dysfunction-associated steatotic liver disease (MASLD). In humans and mice, the cellular heterogeneity and diverse function of hepatic macrophages in MASH have...
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2025-01-01
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| author | Xiaoming Xin Yaohua Ni Jing Wang Fenglin Wu Meichen Liu Lingjuan Wu Jiaxing Dai Chenglin Wu Xiaolei Song Wang Zhang Guangrui Yang Ruling Shen Xianmin Zhu |
| author_facet | Xiaoming Xin Yaohua Ni Jing Wang Fenglin Wu Meichen Liu Lingjuan Wu Jiaxing Dai Chenglin Wu Xiaolei Song Wang Zhang Guangrui Yang Ruling Shen Xianmin Zhu |
| author_sort | Xiaoming Xin |
| collection | DOAJ |
| description | Macrophages play important roles in metabolic dysfunction-associated steatohepatitis (MASH), an advanced and inflammatory stage of metabolic dysfunction-associated steatotic liver disease (MASLD). In humans and mice, the cellular heterogeneity and diverse function of hepatic macrophages in MASH have been investigated by single cell RNA sequencing (scRNA-seq). However, little is known about their roles in rats. Here, we collected liver tissues at the postnatal week 16, when our previously characterized <i>Lep<sup>∆I14/∆I14</sup></i> rats developed MASH phenotypes. By scRNA-seq, we found an increase in the number of macrophages and endothelial cells and a decrease in that of NK and B cells. Hepatic macrophages in rats underwent a unique M1 to M2 transition without expression of the classical markers such as Arg1 and Nos2, except for Cd163. Lipid-associated macrophages (LAMs) were increased, which could be detected by the antibody against Cd63. In the microenvironment, macrophages had an increased number of interactions with hepatocytes, myofibroblasts, T cells, neutrophils, and dendritic cells, while their interaction strengths remained unchanged. Finally, the macrophage migration inhibitory factor (MIF) pathway was identified as the top upregulated cell-communication pathway in MASH. In conclusion, we dissected hepatic macrophage dynamics during MASH at single cell resolution and provided fundamental tools for the investigation of MASH in rat models. |
| format | Article |
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| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| spelling | doaj-art-cd2612b259d1460bbdd130ed2321d6ed2025-01-24T13:26:40ZengMDPI AGCells2073-44092025-01-011429610.3390/cells14020096Single-Cell RNA Sequencing Reveals Macrophage Dynamics During MASH in <i>Leptin</i>-Deficient RatsXiaoming Xin0Yaohua Ni1Jing Wang2Fenglin Wu3Meichen Liu4Lingjuan Wu5Jiaxing Dai6Chenglin Wu7Xiaolei Song8Wang Zhang9Guangrui Yang10Ruling Shen11Xianmin Zhu12School of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai 201318, ChinaSchool of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai 201318, ChinaSchool of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai 201318, ChinaSchool of Clinical Medicine, Shanghai University of Medicine and Health Sciences, Shanghai 201318, ChinaSchool of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai 201318, ChinaSchool of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai 201318, ChinaSchool of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai 201318, ChinaSchool of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai 201318, ChinaSchool of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai 201318, ChinaShanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, ChinaSchool of Clinical Medicine, Shanghai University of Medicine and Health Sciences, Shanghai 201318, ChinaShanghai Academy of Sciences & Technology Institute of Model Animals Transformation, Shanghai Laboratory Animal Research Center, Shanghai 201203, ChinaShanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, ChinaMacrophages play important roles in metabolic dysfunction-associated steatohepatitis (MASH), an advanced and inflammatory stage of metabolic dysfunction-associated steatotic liver disease (MASLD). In humans and mice, the cellular heterogeneity and diverse function of hepatic macrophages in MASH have been investigated by single cell RNA sequencing (scRNA-seq). However, little is known about their roles in rats. Here, we collected liver tissues at the postnatal week 16, when our previously characterized <i>Lep<sup>∆I14/∆I14</sup></i> rats developed MASH phenotypes. By scRNA-seq, we found an increase in the number of macrophages and endothelial cells and a decrease in that of NK and B cells. Hepatic macrophages in rats underwent a unique M1 to M2 transition without expression of the classical markers such as Arg1 and Nos2, except for Cd163. Lipid-associated macrophages (LAMs) were increased, which could be detected by the antibody against Cd63. In the microenvironment, macrophages had an increased number of interactions with hepatocytes, myofibroblasts, T cells, neutrophils, and dendritic cells, while their interaction strengths remained unchanged. Finally, the macrophage migration inhibitory factor (MIF) pathway was identified as the top upregulated cell-communication pathway in MASH. In conclusion, we dissected hepatic macrophage dynamics during MASH at single cell resolution and provided fundamental tools for the investigation of MASH in rat models.https://www.mdpi.com/2073-4409/14/2/96MASHinflammationsingle cell RNA sequencingmacrophagerat |
| spellingShingle | Xiaoming Xin Yaohua Ni Jing Wang Fenglin Wu Meichen Liu Lingjuan Wu Jiaxing Dai Chenglin Wu Xiaolei Song Wang Zhang Guangrui Yang Ruling Shen Xianmin Zhu Single-Cell RNA Sequencing Reveals Macrophage Dynamics During MASH in <i>Leptin</i>-Deficient Rats Cells MASH inflammation single cell RNA sequencing macrophage rat |
| title | Single-Cell RNA Sequencing Reveals Macrophage Dynamics During MASH in <i>Leptin</i>-Deficient Rats |
| title_full | Single-Cell RNA Sequencing Reveals Macrophage Dynamics During MASH in <i>Leptin</i>-Deficient Rats |
| title_fullStr | Single-Cell RNA Sequencing Reveals Macrophage Dynamics During MASH in <i>Leptin</i>-Deficient Rats |
| title_full_unstemmed | Single-Cell RNA Sequencing Reveals Macrophage Dynamics During MASH in <i>Leptin</i>-Deficient Rats |
| title_short | Single-Cell RNA Sequencing Reveals Macrophage Dynamics During MASH in <i>Leptin</i>-Deficient Rats |
| title_sort | single cell rna sequencing reveals macrophage dynamics during mash in i leptin i deficient rats |
| topic | MASH inflammation single cell RNA sequencing macrophage rat |
| url | https://www.mdpi.com/2073-4409/14/2/96 |
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