Single-Cell RNA Sequencing and Quantitative Proteomics Analysis Elucidate Marker Genes and Molecular Mechanisms in Hypoplastic Left Heart Patients With Heart Failure

Ma, Li; Zhou, Na; Zou, Rongjun; Shi, Wu; Luo, Yuanyuan; Du, Na; Zhong, Jing; Zhao, Xiaodong; Chen, Xinxin; Xia, Huimin; Qin, Xianyu

doi:10.3389/fcell.2021.617853

Cited by 5 publications

(2 citation statements)

References 54 publications

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“…Although the MKL1 f/f mice seem to exhibit similar phenotypes in different models of tissue fibrosis, it is unlikely that the transcriptomes of cardiac fibroblasts, pulmonary fibroblasts, and renal fibroblasts might be uniformly altered by the loss of MKL1. Recent advances in single-cell RNAsequencing have greatly facilitated the fine-dissecting the dynamic transcriptomic changes in a wide ranges of tissues and organs (Fu et al, 2021;Liang et al, 2021;Ma et al, 2021;Xie et al, 2021;Zhao et al, 2021). Therefore, a comparison of gene expression profiles of the MKL1-null fibroblasts using this stateof-the-art technique in different organs could shed additional insight on the mode of action for MKL1.…”

Section: Discussionmentioning

confidence: 99%

Resident Fibroblast MKL1 Is Sufficient to Drive Pro-fibrogenic Response in Mice

Huang

Shao

Liu

et al. 2022

Front. Cell Dev. Biol.

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Fibrosis is an evolutionarily conserved pathophysiological process serving bifurcated purposes. On the one hand, fibrosis is essential for wound healing and contributes to the preservation of organ function. On the other hand, aberrant fibrogenic response may lead to tissue remodeling and precipitate organ failure. Recently lineage tracing studies have shown that resident fibroblasts are the primary mediator of fibrosis taking place in key organs such as the heart, the lungs, and the kidneys. Megakaryocytic leukemia 1 (MKL1) is transcriptional regulator involved in tissue fibrosis. Here we generated resident fibroblast conditional MKL1 knockout (CKO) mice by crossing the Mkl1f/f mice to the Col1a2-CreERT2 mice. Models of cardiac fibrosis, pulmonary fibrosis, and renal fibrosis were reproduced in the CKO mice and wild type (WT) littermates. Compared to the WT mice, the CKO mice displayed across-the-board attenuation of fibrosis in different models. Our data cement the pivotal role MKL1 plays in tissue fibrosis but point to the cellular origin from which MKL1 exerts its pro-fibrogenic effects.

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Section: Discussionmentioning

confidence: 99%

Resident Fibroblast MKL1 Is Sufficient to Drive Pro-fibrogenic Response in Mice

Huang

Shao

Liu

et al. 2022

Front. Cell Dev. Biol.

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“…Single-cell RNA sequencing can simultaneously study the expression levels of multiple genes in thousands of single cells 16 . It has been widely used in the identi cation of various cell types in the pathological process of various diseases, such as cardiomyocytes 17 Tumor cells 18 Knee meniscus 19 , Liver brosis 20 . In addition, scRNA-seq has been able to explore different heterogeneity in the population of single cell subtypes.…”

Section: Introductionmentioning

confidence: 99%

Single-cell RNA sequencing and molecular docking reveal sinomenine can treat postherpetic neuralgia by regulating the expression of MMP2

Zhang

Zhao

2022

Preprint

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Objective: The pathogenesis of postherpetic neuralgia is not clear, the pain is severe, the duration is long, and the treatment effect is poor. We explored the potential mechanism of sinomenine in the treatment of postherpetic neuralgia based on single-cell sequencing and molecular docking technology and provided a theoretical basis for studying the pathogenesis of postherpetic neuralgia. Methods: Based on single-cell sequencing analysis and bioinformatics, the possible pain-causing factors of postherpetic neuralgia were identified, and the interaction between sinomenine and the target protein was analyzed using the molecular docking technique. First, the genes related to sinomenine and postherpetic neuralgia were found through various databases. Then, single-cell gene sequencing was used to identify pain-related marker genes and their role in cell subsets. The intersection of the differentially expressed (|LogFC|>1) marker gene and the postherpetic neuralgia-related genes in single-cell sequencing was used as the postherpetic neuralgia pain-causing gene set. Intersection of sinomenine and hub genes was used to identify the target genes that interact with each other, and sinomenine was molecularly docked with the target genes. Results: A total of 2524 postherpetic neuralgia-related genes and 43 sinomenine-related genes were identified through Genecard, CTD, and the GEO database. Single-cell gene sequencing was performed and revealed a total of 680 marker genes between pain and pain-free cell populations |logFC|>1. Pain-associated subpopulations were annotated mainly with microglia and astrocytes. And there were 125 intersection genes associated with postherpetic neuralgia. These genes were associated with the development of postherpetic neuralgia. 42 hub gene were identified from these crossover genes. MMP2 is the common gene of hub genes and sinomenine-related genes. Molecular docking discovers better affinity and stability between sinomenine and MMP2 protein. Conclusion: This study combined single cell analysis, bioinformatics and molecular docking to identify MMP2 as a potential target for sinomenine in the treatment of postherpetic neuralgia, which may act on microglia to alleviate pain by regulating the neuroinflammatory response and ion pathways.

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Single-cell transcriptome sequencing of macrophages in common cardiovascular diseases

Wang

et al. 2023

Journal of Leukocyte Biology

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Macrophages are strategically located throughout the body at key sites in the immune system. A key feature in atherosclerosis is the uptake and accumulation of lipoproteins by arterial macrophages, leading to the formation of foam cells. After myocardial infarction, macrophages derived from monocytes infiltrate the infarcted heart. Macrophages are also closely related to adverse remodeling after heart failure. An in-depth understanding of the functions and characteristics of macrophages is required to study heart health and pathophysiological processes; however, the heterogeneity and plasticity explained by the classic M1/M2 macrophage paradigm are too limited. Single-cell sequencing is a high-throughput sequencing technique that enables the sequencing of the genome or transcriptome of a single cell. It effectively complements the heterogeneity of gene expression in a single cell that is ignored by conventional sequencing and can give valuable insights into the development of complex diseases. In the present review, we summarize the available research on the application of single-cell transcriptome sequencing to study the changes in macrophages during common cardiovascular diseases, such as atherosclerosis, myocardial infarction, and heart failure. This article also discusses the contribution of this knowledge to understanding the pathogenesis, development, diagnosis, and treatment of heart diseases.

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Single-Cell RNA Sequencing and Quantitative Proteomics Analysis Elucidate Marker Genes and Molecular Mechanisms in Hypoplastic Left Heart Patients With Heart Failure

Cited by 5 publications

References 54 publications

Resident Fibroblast MKL1 Is Sufficient to Drive Pro-fibrogenic Response in Mice

Resident Fibroblast MKL1 Is Sufficient to Drive Pro-fibrogenic Response in Mice

Single-cell RNA sequencing and molecular docking reveal sinomenine can treat postherpetic neuralgia by regulating the expression of MMP2

Single-cell transcriptome sequencing of macrophages in common cardiovascular diseases

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