Single-Cell RNA Sequencing Reveals Smooth Muscle Cells Heterogeneity in Experimental Aortic Dissection

Xu, Cheng; Liu, Xiaowei; Fang, Xiaoxin; Yu, Lei; Lau, Hui Chong; Li, Danlei; Liu, Xiaoman; Li, Haili; Ren, Justin; Xu, Baohui; Jiang, Jianjun; Tang, Lijiang; Chen, Xiaofeng

doi:10.3389/fgene.2022.836593

Cited by 7 publications

(8 citation statements)

References 42 publications

(44 reference statements)

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“…Single-cell RNA sequencing (scRNA-seq) technology can observe changes that occur in different cell types [22]. Xu et al identified 15 cell clusters and nine cell types in AD mouse tissues by scRNA-seq, and they found that the type and relative number of SMCs changed significantly in AD model mouse tissues [23].…”

Section: Introductionmentioning

confidence: 99%

Identification and Analysis of Hub Genes and Immune Cells Associated with the Formation of Acute Aortic Dissection

Zhong

Cai

Zhou

et al. 2023

Computational and Mathematical Methods in Medicine

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Background. Acute type A aortic dissection (AAD) is a catastrophic disease with high mortality, but the pathogenesis has not been fully elucidated. This study is aimed at identifying hub genes and immune cells associated with the pathogenesis of AAD. Methods. The datasets were downloaded from Gene Expression Omnibus (GEO). Gene Set Enrichment Analysis (GSEA), gene set variation analysis (GSVA), and differential analysis were performed. The differentially expressed genes (DEGs) were intersected with specific genes collected from MSigDB. The gene function and pathway enrichment analysis were also performed on intersecting genes. The key modules were selected by weighted gene coexpression network analysis (WGCNA). Hub genes were identified by least absolute shrinkage and selection operator (LASSO) analysis and were verified in the metadataset. The immune cell infiltration was analyzed by CIBERSORT, and the relationship between hub genes and immune cells was performed by Pearson’s correlation analysis. The single-cell RNA sequencing (scRNA-seq) dataset was used to verify the differences in DNA damage and repair signaling pathways and hub genes in different cell types. Results. The results of GSEA and GSVA indicated that DNA damage and repair processes were activated in the occurrence of AAD. The gene function and pathway enrichment analysis on differentially expressed DNA damage- and repair-related genes showed that these genes were mainly involved in the regulation of the cell cycle process, cellular response to DNA damage stimulus, response to wounding, p53 signaling pathway, and cellular senescence. Three key modules were identified by WGCNA. Five genes were screened as hub genes, including CDK2, EIF4A1, GLRX, NNMT, and SLCO2A1. Naive B cells and Gamma delta T cells (γδ T cells) were decreased in AAD, but monocytes and M0 macrophages were increased. scRNA-seq analysis included that DNA damage and repair processes were activated in smooth muscle cells (SMCs), tissue stem cells, and monocytes in the aortic wall of patients with AAD. Conclusions. Our results suggested that DNA damage- and repair-related genes may be involved in the occurrence of AAD by regulating many biological processes. The hub genes and immune cells reported in this study also increase the understanding of AAD.

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Section: Introductionmentioning

confidence: 99%

Identification and Analysis of Hub Genes and Immune Cells Associated with the Formation of Acute Aortic Dissection

Zhong

Cai

Zhou

et al. 2023

Computational and Mathematical Methods in Medicine

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“…51,52 There are multiform phenotypes in aortic aneurysm specimens, such as contractile VSMC, mesenchymal-like VSMC, macrophage-like VSMC and fibroblast-like VSMC. 53 Among them, mesenchymal-like VSMC and fibroblast-like VSMC probably play a role in repairing aortic dissection and aortic aneurysm, while macrophage-like VSMC not only has phagocytic function, but also interacts positively with immune cells, recruits monocytes and lymphocytes, stimulate them to migrate to aortic wall and exert their pro-inflammatory function. 54 In this study, M1 macrophages may induce phenotypic transformation of MOVAS cells, but it is not verified whether this is associated with a variety of phenotypes such as macrophage-like VSMC and fibroblast-like VSMC.…”

Section: Discussionmentioning

confidence: 99%

MIF Regulates M1 Macrophage Polarization via CD74/CXCR2/JNK Pathway and Mediates Aortic Dissection in Mice

Wang,

et al. 2023

Preprint

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Background: Macrophage polarization and VSMC phenotypic switch are important features and critical targets in the progression of Aortic dissection (AD). High expression of MIF in aortic and blood specimens has been observed in patients with AD, but its precise function and mechanism in AD are unknown. We aimed to clarify whether MIF mediates the development of aortic dissection via modulation of M1 macrophage polarization. Methods: Based on the BAPN/Ang II-induced acute aortic dissection model and by intraperitoneal injection of the MIF antagonist ISO-1 to inhibit MIF activity in mice. We assayed macrophage infiltration, polarization, and VSMC phenotypic switching in the aorta of mice in each group. Further, we evaluated the polarizing effects of MIF on RAW264.7 cells directly or indirectly in vitro experiments and explored the specific cellular signaling pathways that mediate its function. At last, we evaluated the role and possible mechanisms of RAW264.7 cells with different degrees of polarization in inducing phenotypic switching of MOVAS cells based on a model of indirect co-culture. Results: Pharmacological inhibition of MIF decreased the incidence of aortic dissection and attenuated aortic vascular remodeling in mice by reducing M1 macrophage infiltration in aorta. In addition, we demonstrated that MIF could activate the intracellular JNK/c-Jun signaling pathway by targeting the CD74/CXCR2 receptor, promote M1 polarization and upregulate the expression of the M1 macrophage markers, iNOS, IL-18, and CD86 in RAW264.7 cells. Further experiments confirmed that upon co-culture with MIF-induced M1 macrophages, the NF-?B pathway was activated in MOVAS cells, inducing the onset of phenotypic switch and apoptosis. Conclusions: The results indicated that MIF mediated macrophage polarization and regulated the progression of aortic dissection, which provided new scientific evidence for the pathogenesis of aortic dissection, and also suggested that MIF may be a potential preventive and therapeutic target for aortic dissection and aortic-related diseases.

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“…The differentially expressed genes were uncovered using the Model-based Analysis of Single-cell Transcriptomics, 23 based on the following criteria: |log 2 (fold change)| 0.585 or greater, q value 0.05 or less, and the percentage of cells in the specific cluster greater than 25%. 24 We generated the heatmaps of differentially expressed genes using the z-score approach.…”

Section: Methodsmentioning

confidence: 99%

Single-nucleus Atlas of Sevoflurane-induced Hippocampal Cell Type– and Sex-specific Effects during Development in Mice

et al. 2023

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Background Multiple neonatal exposures to sevoflurane induce neurocognitive dysfunctions in rodents. The lack of cell-type specific information following sevoflurane exposure limits the mechanistic understanding of these effects. In this study, we tested the hypothesis that sevoflurane exposures alter the atlas of hippocampal cell clusters and have neuronal and non-neuronal cell-type specific effects in mice of both sexes. Methods Neonatal mice were exposed to 3% sevoflurane for 2 hours at postnatal days 6, 8, and 10 and analysed for the exposure effects at postnatal day 37. Single-nucleus RNA sequencing was performed in the hippocampus followed by in situ hybridization to validate the results of RNA sequencing. Morris Water Maze test was performed to test neurocognitive function. Results We found sex-specific distribution of hippocampal cell types in control mice alongside cell-type- and sex-specific effects of sevoflurane exposure on distinct hippocampal cell populations. There were important changes in male but not in female mice following sevoflurane exposure regarding the proportions of CA1 neurons (control vs sevoflurane, males: 79.9% vs 32.3%; females: 27.3% vs 24.3%), dentate gyrus (males: 4.2% vs 23.4%; females: 36.2% vs 35.8%), and oligodendrocytes (males: 0.6% vs 6.9%; females: 5.9% vs 7.8%). In male but not in female mice, sevoflurane altered the number of significantly enriched ligand-receptor pairs in the CA1, CA3 and dente gyrus trisynaptic circuit (control vs sevoflurane, CA1-CA3: 18 vs 42 in males and 15 vs 21 in females; CA1-dentate gyrus: 21 vs 35 in males and 12 vs 20 in females; CA3-dentate gyrus: 25 vs 45 in males and 17 vs 20 in females), interfered with dentate gyrus granule cell neurogenesis, hampered microglia differentiation, and decreased CA1 pyramidal cell diversity. Oligodendrocyte differentiation was specifically altered in females with increased expressions of Mbp and Mag. In situ hybridization validated the increased expression of common differentially expressed genes. Conclusions This single-nucleus RNA sequencing study reveals the hippocampal atlas of mice, providing a comprehensive resource for the neuronal and non-neuronal cell-type- and sex-specific effects of sevoflurane during development.

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Single-Cell RNA Sequencing Reveals Smooth Muscle Cells Heterogeneity in Experimental Aortic Dissection

Cited by 7 publications

References 42 publications

Identification and Analysis of Hub Genes and Immune Cells Associated with the Formation of Acute Aortic Dissection

Identification and Analysis of Hub Genes and Immune Cells Associated with the Formation of Acute Aortic Dissection

MIF Regulates M1 Macrophage Polarization via CD74/CXCR2/JNK Pathway and Mediates Aortic Dissection in Mice

Single-nucleus Atlas of Sevoflurane-induced Hippocampal Cell Type– and Sex-specific Effects during Development in Mice

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