Song Yiran, Wang Li, Wang Haofei, Ma Hong, Xu Jun, Liu Jiandong, Qian Li
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
McAllister Heart Institute, University of North Carolina, Chapel Hill, NC 27599, USA.
iScience. 2024 Nov 28;27(12):111469. doi: 10.1016/j.isci.2024.111469. eCollection 2024 Dec 20.
To understand heart aging at the single-cell level, we employed single-cell dual omics (scRNA-seq and scATAC-seq) in profiling non-myocytes (non-CMs) from young, middle-aged, and elderly mice. Non-CMs, vital in heart development, physiology, and pathology, are understudied compared to cardiomyocytes. Our analysis revealed aging response heterogeneity and its dynamics over time. Immune cells, notably macrophages and neutrophils, showed significant aging alterations, while endothelial cells displayed moderate changes. We identified distinct aging signatures within the cell type, including differential gene expression, transcription factor activity, and motif variation. Sub-cluster analysis revealed intra-cell type heterogeneity, characterized by diverse aging patterns. The senescence-associated secretory phenotype emerged as a key aging-related phenotype. Moreover, aging significantly influenced cell-cell communication, especially impacting a fibroblast sub-cluster with high expression of ERBB4. This study elucidates the complex cellular and molecular landscape of cardiac aging and offers guidance for potential therapeutic avenues to treat aging-related heart diseases.
为了在单细胞水平上理解心脏衰老，我们采用单细胞双组学技术（scRNA-seq和scATAC-seq）对年轻、中年和老年小鼠的非心肌细胞（non-CMs）进行分析。与心肌细胞相比，非心肌细胞在心脏发育、生理和病理过程中至关重要，但对其研究较少。我们的分析揭示了衰老反应的异质性及其随时间的动态变化。免疫细胞，特别是巨噬细胞和中性粒细胞，表现出显著的衰老改变，而内皮细胞则显示出适度的变化。我们在细胞类型中鉴定出不同的衰老特征，包括差异基因表达、转录因子活性和基序变异。亚群分析揭示了细胞内类型的异质性，其特征是不同的衰老模式。衰老相关分泌表型成为关键的衰老相关表型。此外，衰老显著影响细胞间通讯，尤其影响高表达ERBB4的成纤维细胞亚群。这项研究阐明了心脏衰老复杂的细胞和分子景观，并为治疗衰老相关心脏病的潜在治疗途径提供了指导。
