College of Life Sciences, Biomedical Pioneering Innovation Center, Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing, China.
Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Peking University, Beijing, China.
Cell Prolif. 2024 Mar;57(3):e13557. doi: 10.1111/cpr.13557. Epub 2023 Sep 28.
Hypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disease, which can cause heart failure and lead to death. In this study, we performed high-resolution single-cell RNA-sequencing of 2115 individual cardiomyocytes obtained from HCM patients and normal controls. Signature up- and down-regulated genes in HCM were identified by integrative analysis across 37 patients and 41 controls from our data and published human single-cell and single-nucleus RNA-seq datasets, which were further classified into gene modules by single-cell co-expression analysis. Using our high-resolution dataset, we also investigated the heterogeneity among individual cardiomyocytes and revealed five distinct clusters within HCM cardiomyocytes. Interestingly, we showed that some extracellular matrix (ECM) genes were up-regulated in the HCM cardiomyocytes, suggesting that they play a role in cardiac remodelling. Taken together, our study comprehensively profiled the transcriptomic programs of HCM cardiomyocytes and provided insights into molecular mechanisms underlying the pathogenesis of HCM.
肥厚型心肌病（HCM）是一种常见的遗传性心血管疾病，可导致心力衰竭并导致死亡。在这项研究中，我们对 2115 个来自 HCM 患者和正常对照者的单个心肌细胞进行了高分辨率单细胞 RNA 测序。通过对来自我们的数据和已发表的人类单细胞和单核 RNA-seq 数据集的 37 名患者和 41 名对照者的综合分析，确定了 HCM 中上调和下调的特征基因，这些基因进一步通过单细胞共表达分析被分类为基因模块。利用我们的高分辨率数据集，我们还研究了个体心肌细胞之间的异质性，并在 HCM 心肌细胞中揭示了五个不同的簇。有趣的是，我们发现一些细胞外基质（ECM）基因在 HCM 心肌细胞中上调，提示它们在心脏重构中发挥作用。总之，我们的研究全面描绘了 HCM 心肌细胞的转录组图谱，并为 HCM 发病机制的分子机制提供了新的见解。
