Cao Lizhi, Chang Rui, Wang Xiaoying, Shen Junwei, Yang Zhifang, Ma Linlin, Li Yanfei
Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, China.
School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China.
Mol Biotechnol. 2025 Jun 9. doi: 10.1007/s12033-025-01443-3.
Cardiomyocytes, pivotal for heart contractility, are categorized into atrial (aCM) and ventricular (vCM) subtypes, each playing distinct roles in modulating blood flow, electrical signal conduction, pump function, and energy metabolism. Recent advancements in single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics have enhanced our understanding of cellular heterogeneity and intercellular communication within cardiac tissues. This study integrates scRNA-seq with spatial mapping to elucidate the spatial distribution and intercellular communication of aCM and vCM, focusing on their roles in energy metabolism, pump function, and regulatory functions. We performed scRNA-seq on isolated cardiac cells, followed by data normalization, PCA, and t-SNE clustering, identifying distinct cardiomyocyte subclusters. Ligand-receptor interaction analyses were conducted to explore cellular communication networks, and annotated single-cell data were projected onto heart tissue sections using spatial transcriptomics. Our results revealed distinct spatial distributions: vCM subclusters (vCM-1, vCM-2, vCM-3) predominantly occupied ventricular regions, while aCM subclusters (aCM-1, aCM-2) were primarily located in atrial regions with an increased presence of fibroblasts near atria. Igf2-Igf2r and Vegfb-Vegfr1 mediated communications were prominent in both regions, with extensive interactions between aCM-2 and vCM subclusters. This integration of scRNA-seq and spatial transcriptomics provides a comprehensive overview of cardiac tissue organization and intercellular communication, elucidating critical roles of vCM in energy metabolism and pump function, and aCM in regulating blood flow and electrical conduction. Understanding these interactions in anatomical context enhances our grasp of cardiac function complexity and identifies new therapeutic targets for cardiac diseases.
心肌细胞对心脏收缩至关重要，可分为心房（aCM）和心室（vCM）亚型，它们在调节血流、电信号传导、泵功能和能量代谢方面发挥着不同作用。单细胞RNA测序（scRNA-seq）和空间转录组学的最新进展增进了我们对心脏组织内细胞异质性和细胞间通讯的理解。本研究将scRNA-seq与空间图谱相结合，以阐明aCM和vCM的空间分布及细胞间通讯，重点关注它们在能量代谢、泵功能和调节功能中的作用。我们对分离的心脏细胞进行了scRNA-seq，随后进行数据归一化、主成分分析（PCA）和t-SNE聚类，识别出不同的心肌细胞亚群。进行配体-受体相互作用分析以探索细胞通讯网络，并使用空间转录组学将注释后的单细胞数据投影到心脏组织切片上。我们的结果揭示了不同的空间分布：vCM亚群（vCM-1、vCM-2、vCM-3）主要占据心室区域，而aCM亚群（aCM-1、aCM-2）主要位于心房区域，心房附近的成纤维细胞数量增加。Igf2-Igf2r和Vegfb-Vegfr1介导的通讯在两个区域都很突出，aCM-2和vCM亚群之间存在广泛的相互作用。scRNA-seq与空间转录组学的这种整合提供了心脏组织结构和细胞间通讯的全面概述，阐明了vCM在能量代谢和泵功能中的关键作用，以及aCM在调节血流和电传导中的关键作用。在解剖学背景下理解这些相互作用可增强我们对心脏功能复杂性的理解，并确定心脏病的新治疗靶点。
