The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China.
Department of Cardiology, Jinan Central Hospital Affiliated to Shandong University, Jinan, China.
J Cell Mol Med. 2021 Oct;25(20):9660-9673. doi: 10.1111/jcmm.16914. Epub 2021 Sep 12.
This study aimed to characterize the cells and gene expression landscape in atrial septal defect (ASD). We performed single-cell RNA sequencing of cells derived from cardiac tissue of an ASD patient. Unsupervised clustering analysis was performed to identify different cell populations, followed by the investigation of the cellular crosstalk by analysing ligand-receptor interactions across cell types. Finally, differences between ASD and normal samples for all cell types were further investigated. An expression matrix of 18,411 genes in 6487 cells was obtained and used in this analysis. Five cell types, including cardiomyocytes, endothelial cells, smooth muscle cells, fibroblasts and macrophages were identified. ASD showed a decreased proportion of cardiomyocytes and an increased proportion of fibroblasts. There was more cellular crosstalk among cardiomyocytes, fibroblasts and macrophages, especially between fibroblast and macrophage. For all cell types, the majority of the DEGs were downregulated in ASD samples. For cardiomyocytes, there were 199 DEGs (42 upregulated and 157 downregulated) between ASD and normal samples. PPI analysis showed that cardiomyocyte marker gene FABP4 interacted with FOS, while FOS showed interaction with NPPA. Cell trajectory analysis showed that FABP4, FOS, and NPPA showed different expression changes along the pseudotime trajectory. Our results showed that single-cell RNA sequencing provides a powerful tool to study DEG profiles in the cell subpopulations of interest at the single-cell level. These findings enhance the understanding of the underlying mechanisms of ASD at both the cellular and molecular level and highlight potential targets for the treatment of ASD.
本研究旨在对房间隔缺损（ASD）中的细胞和基因表达图谱进行特征分析。我们对一名 ASD 患者的心脏组织来源的细胞进行了单细胞 RNA 测序。采用无监督聚类分析来鉴定不同的细胞群体，然后通过分析细胞类型之间的配体-受体相互作用来研究细胞间的相互作用。最后，进一步研究了所有细胞类型中 ASD 与正常样本之间的差异。获得了包含 6487 个细胞的 18411 个基因的表达矩阵，并用于本分析。鉴定出了 5 种细胞类型，包括心肌细胞、内皮细胞、平滑肌细胞、成纤维细胞和巨噬细胞。ASD 表现为心肌细胞比例降低，成纤维细胞比例增加。心肌细胞、成纤维细胞和巨噬细胞之间的细胞间相互作用增加，尤其是成纤维细胞和巨噬细胞之间。对于所有细胞类型，ASD 样本中的大多数差异表达基因（DEG）下调。在 ASD 和正常样本之间，心肌细胞有 199 个 DEG（42 个上调和 157 个下调）。PPI 分析显示，心肌细胞标记基因 FABP4 与 FOS 相互作用，而 FOS 与 NPPA 相互作用。细胞轨迹分析显示，FABP4、FOS 和 NPPA 在沿着伪时间轨迹表达时表现出不同的变化。我们的结果表明，单细胞 RNA 测序为在单细胞水平上研究感兴趣的细胞亚群中的 DEG 图谱提供了强大的工具。这些发现增强了我们对细胞和分子水平上 ASD 潜在机制的理解，并突出了 ASD 治疗的潜在靶点。
