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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 Lep\u2206I14\/\u2206I14 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.<\/jats:p>","DOI":"10.3390\/cells14020096","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T08:03:05Z","timestamp":1736496185000},"page":"96","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Single-Cell RNA Sequencing Reveals Macrophage Dynamics During MASH in Leptin-Deficient Rats"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2589-2004","authenticated-orcid":false,"given":"Xiaoming","family":"Xin","sequence":"first","affiliation":[{"name":"School of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaohua","family":"Ni","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenglin","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meichen","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingjuan","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2456-3590","authenticated-orcid":false,"given":"Jiaxing","family":"Dai","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenglin","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6590-3062","authenticated-orcid":false,"given":"Xiaolei","family":"Song","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangrui","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7529-810X","authenticated-orcid":false,"given":"Ruling","family":"Shen","sequence":"additional","affiliation":[{"name":"Shanghai Academy of Sciences & Technology Institute of Model Animals Transformation, Shanghai Laboratory Animal Research Center, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1405-9700","authenticated-orcid":false,"given":"Xianmin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China"},{"name":"Shanghai Academy of Sciences & Technology Institute of Model Animals Transformation, Shanghai Laboratory Animal Research Center, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s41575-019-0144-8","article-title":"Past, present and future perspectives in nonalcoholic fatty liver disease","volume":"16","author":"Sanyal","year":"2019","journal-title":"Nat. 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