Single-cell transcriptomes identifies characteristic features of mouse macrophages in liver Mallory-Denk bodies formation

Zhang, Rong; Zhong, Bei; He, Jiashan; Yang, Xinyu; He, Menghua; Zeng, Wuyi; Pan, Jiayi; Fang, Zixuan; Jia, Jiangtao; Liu, Hui

doi:10.1016/j.yexmp.2022.104811

Cited by 4 publications

(4 citation statements)

References 54 publications

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“…Combining new technologies, such as spatial transcriptomics, will further deepen our understanding of the pathogenesis of NAFLD. The application of scRNA-seq and SM-Omics in humans [ [157] , [158] , [159] , [160] , [161] ], mice [ [162] , [163] , [164] , [165] , [166] , [167] , [168] ], and minipigs [ 169 ] has yielded many valuable results in the field of NAFLD research ( Fig. 5 ).…”

Section: The Application Of Scm-omics and Sm-omics In Nafldmentioning

confidence: 99%

“…Here, we summarize and categorize the studies applying SCM-Omics and SM-Omics techniques in NAFLD ( Table S3 ). At present, the main sequencing methods used in NAFLD research include scRNA-seq [ [157] , [158] , [159] ], snRNA-seq [ [159] , [160] , [161] ], and spatial transcriptome sequencing [ 159 , 162 ]. SCM-Omics and SM-Omics technologies have provided new research directions for truly understanding the heterogeneity and complexity of NAFLD disease progression, but the application of multi-omics analysis remains in the stage of continuous renewal and development.…”

Section: The Application Of Scm-omics and Sm-omics In Nafldmentioning

confidence: 99%

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New discoveries in the field of metabolism by applying single-cell and spatial omics

Xie

Gao

Zhou

et al. 2023

Journal of Pharmaceutical Analysis

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Section: The Application Of Scm-omics and Sm-omics In Nafldmentioning

confidence: 99%

Section: The Application Of Scm-omics and Sm-omics In Nafldmentioning

confidence: 99%

New discoveries in the field of metabolism by applying single-cell and spatial omics

Xie

Gao

Zhou

et al. 2023

Journal of Pharmaceutical Analysis

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“…[1,2] In ALD, multiple liver cell types are impacted by alcohol exposure; however, it is not clear if the effects on individual cells are direct effects of alcohol or a response to alcohol-induced signals from other cells. Advances in technologies such as single-cell sequencing and spatial transcriptomics have revealed new details regarding the complexity of hepatic cell types [3][4][5][6] and have highlighted the importance of cell-cell communication by means of secreted mediators such as peptides, hormones, and cytokines (secretome) in disease development and progression. [7] Recent studies suggest that hepatocytes play a central role in driving ALD and influence the phenotype of nonparenchymal cells in the liver both during disease development [8,9] and resolution.…”

Section: Introductionmentioning

confidence: 99%

Alcohol-induced epigenetic changes prevent fibrosis resolution after alcohol cessation in miceresolution

Schonfeld,

O’Neil,

Weinman

et al. 2023

Hepatology

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Background and aims: Alcohol-associated liver disease (ALD) is a major cause of alcohol related mortality. Recently we identified hepatic demethylases KDM5B and KDM5C as important epigenetic regulators of alcohol response in the liver. In this study we aimed to investigate the role of KDM5-demethylases in ALD resolution. Approach and Results: We showed that alcohol induced liver steatosis rapidly resolved after alcohol cessation. In contrast, fibrosis persisted in the liver for up to 8 weeks after the end of alcohol exposure. Defects in fibrosis resolution were in part due to alcohol-induced KDM5B and KDM5C-dependent epigenetic changes in hepatocytes. Using cell type specific knockout mice, we found that AAV mediated knockout of KDM5B and KDM5C demethylases in hepatocytes at the time of alcohol withdrawal promoted fibrosis resolution. scATAC-seq analysis showed that during ALD resolution epigenetic cell states largely reverted to control conditions. In addition, we found unique epigenetic cell states distinct from both control and alcohol states and identified associated transcriptional regulators including LXRα. In vitro and in vivo analysis confirmed that knockout of KDM5B and KDM5C demethylases promoted LXRα activity, likely through regulation of oxysterol biosynthesis, and this activity was critical for the fibrosis resolution process. Reduced LXR activity by small molecule inhibitors prevented fibrosis resolution in KDM5-deficient mice. Conclusion: In summary, KDM5B and KDM5C demethylases prevent liver fibrosis resolution after alcohol cessation in part through suppression of LXR activity.

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“…C-C chemokine receptor types 2 (CCR2) and C-C chemokine receptor types 5 (CCR5) and their respective ligands play important roles in the recruitment of monocytes and macrophages to inflammation sites [1][2][3][4][5][6][7][8][9][10][11]. A protein called FROUNT (NUP85, Nucle-oporin85) was shown to promote the phosphatidylinositol-3-OH kinase (PI3K) cascade and cell migration by binding directly to the intracellular C-terminal region of CCR2 and CCR5 [12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Disulfiram Ophthalmic Solution Inhibited Macrophage Infiltration by Suppressing Macrophage Pseudopodia Formation in a Rat Corneal Alkali Burn Model

Ikebukuro

Arima

Kasamatsu

et al. 2023

IJMS

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FROUNT is an intracellular protein that promotes pseudopodia formation by binding to the chemokine receptors CCR2 and CCR5 on macrophages. Recently, disulfiram (DSF), a drug treatment for alcoholism, was found to have FROUNT inhibitory activity. In this study, we investigated the effect of DSF eye drops in a rat corneal alkali burn model. After alkali burn, 0.5% DSF eye drops (DSF group) and vehicle eye drops (Vehicle group) were administered twice daily. Immunohistochemical observations and real-time reverse transcription-polymerase chain reaction (RT-PCR) analyses were performed at 6 h and 1, 4, and 7 days after alkali burn. Results showed a significant decrease in macrophage accumulation in the cornea in the DSF group, but no difference in neutrophils. RT-PCR showed decreased expression of macrophage-associated cytokines in the DSF group. Corneal scarring and neovascularization were also suppressed in the DSF group. Low-vacuum scanning electron microscopy imaging showed that macrophage length was significantly shorter in the DSF group, reflecting the reduced extension of pseudopodia. These results suggest that DSF inhibited macrophage infiltration by suppressing macrophage pseudopodia formation.

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Single-cell transcriptomes identifies characteristic features of mouse macrophages in liver Mallory-Denk bodies formation

Cited by 4 publications

References 54 publications

New discoveries in the field of metabolism by applying single-cell and spatial omics

New discoveries in the field of metabolism by applying single-cell and spatial omics

Alcohol-induced epigenetic changes prevent fibrosis resolution after alcohol cessation in miceresolution

Disulfiram Ophthalmic Solution Inhibited Macrophage Infiltration by Suppressing Macrophage Pseudopodia Formation in a Rat Corneal Alkali Burn Model

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