Koenig Andrew L, Shchukina Irina, Amrute Junedh, Andhey Prabhakar S, Zaitsev Konstantin, Lai Lulu, Bajpai Geetika, Bredemeyer Andrea, Smith Gabriella, Jones Cameran, Terrebonne Emily, Rentschler Stacey L, Artyomov Maxim N, Lavine Kory J
Center for Cardiovascular Research, Department of Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, MO, USA.
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Nat Cardiovasc Res. 2022 Mar;1(3):263-280. doi: 10.1038/s44161-022-00028-6. Epub 2022 Mar 16.
Heart failure represents a major cause of morbidity and mortality worldwide. Single-cell transcriptomics have revolutionized our understanding of cell composition and associated gene expression. Through integrated analysis of single-cell and single-nucleus RNA-sequencing data generated from 27 healthy donors and 18 individuals with dilated cardiomyopathy, here we define the cell composition of the healthy and failing human heart. We identify cell-specific transcriptional signatures associated with age and heart failure and reveal the emergence of disease-associated cell states. Notably, cardiomyocytes converge toward common disease-associated cell states, whereas fibroblasts and myeloid cells undergo dramatic diversification. Endothelial cells and pericytes display global transcriptional shifts without changes in cell complexity. Collectively, our findings provide a comprehensive analysis of the cellular and transcriptomic landscape of human heart failure, identify cell type-specific transcriptional programs and disease-associated cell states and establish a valuable resource for the investigation of human heart failure.
心力衰竭是全球发病和死亡的主要原因。单细胞转录组学彻底改变了我们对细胞组成和相关基因表达的理解。通过对27名健康供体和18名扩张型心肌病患者产生的单细胞和单细胞核RNA测序数据进行综合分析，我们在此定义了健康和衰竭人类心脏的细胞组成。我们确定了与年龄和心力衰竭相关的细胞特异性转录特征，并揭示了疾病相关细胞状态的出现。值得注意的是，心肌细胞趋向于常见的疾病相关细胞状态，而成纤维细胞和髓样细胞则经历了显著的多样化。内皮细胞和周细胞表现出整体转录变化，但细胞复杂性没有改变。总体而言，我们的研究结果对人类心力衰竭的细胞和转录组景观进行了全面分析，确定了细胞类型特异性转录程序和疾病相关细胞状态，并为人类心力衰竭的研究建立了宝贵的资源。
