Wan Jingjing, Zhang Zhen, Tian Saisai, Huang Si, Jin Huizi, Liu Xia, Zhang Weidong
School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China; School of Pharmacy, Second Military Medical University, Shanghai, China.
School of Pharmacy, Second Military Medical University, Shanghai, China.
Genomics. 2022 May;114(3):110322. doi: 10.1016/j.ygeno.2022.110322. Epub 2022 Feb 25.
Non-cardiomyocytes (non-CMs) play an important role in the process of cardiac remodeling of chronic heart failure. The mechanism of non-CMs transit and interact with each other remains largely unknown. Here, we try to characterize the cellular landscape of non-CMs in mice with chronic heart failure by using single-cell RNA sequencing (scRNA-seq) and provide potential therapeutic hunts. Cellular and molecular analysis revealed that the most affected cellular types are mainly fibroblasts and endothelial cells. Specially, Fib_0 cluster, the most abundant cluster in fibroblasts, was the only increased one, enriched for collagen synthesis genes such as Adamts4 and Crem, which might be responsible for the fibrosis in cardiac remodeling. End_0 cluster in endothelial cells was also the most abundant and only increased one, which has an effect of blood vessel morphogenesis. Cell communication further confirmed that fibroblasts and endothelial cells are the driving hubs in chronic heart failure. Furthermore, using fibroblasts and endothelial cells as the entry point of CMap technology, histone deacetylation (HDAC) inhibitors and HSP inhibitors were identified as potential anti-heart failure new drugs, which should be evaluated in the future. The combined application of scRNA-seq and CMap might be an effective way to achieve drug repositioning.
非心肌细胞（non-CMs）在慢性心力衰竭心脏重塑过程中发挥着重要作用。非心肌细胞相互转变和相互作用的机制在很大程度上仍不清楚。在此，我们试图通过使用单细胞RNA测序（scRNA-seq）来描绘慢性心力衰竭小鼠中非心肌细胞的细胞图谱，并提供潜在的治疗线索。细胞和分子分析表明，受影响最严重的细胞类型主要是成纤维细胞和内皮细胞。特别地，成纤维细胞中最丰富的簇Fib_0是唯一增加的簇，富含Adamts4和Crem等胶原蛋白合成基因，这可能是心脏重塑中纤维化的原因。内皮细胞中的End_0簇也是最丰富且唯一增加的簇，具有血管形态发生的作用。细胞通讯进一步证实成纤维细胞和内皮细胞是慢性心力衰竭中的驱动枢纽。此外，以成纤维细胞和内皮细胞作为CMap技术的切入点，组蛋白去乙酰化（HDAC）抑制剂和热休克蛋白（HSP）抑制剂被鉴定为潜在的抗心力衰竭新药，未来应进行评估。scRNA-seq和CMap的联合应用可能是实现药物重新定位的有效方法。
