Single-cell sequencing reveals the cardio-protective role of overexpressing Cox7B in hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is an important cause leading to heart failure. Preserving cardiac function particularly in cardiomyocytes (CMs) is essential for improving prognosis in HCM patients. Therefore, understanding single-cell transcriptome characteristics of CMs in HCM would be indispensable to investigate potential therapeutic targets. We applied single-cell tagged reverse transcription (STRT-seq) approach and obtained 338 CM transcriptomes. The human heart samples were collected from HCM patients who had extended septal myectomy and healthy donors. Our results revealed that in nonfailing HCM heart CMs could be categorized into three subsets: high energy synthesis cluster, high cellular metabolism cluster and intermediate cluster. The expression of mitochondrial and electron transport chain (ETC) was up-regulated in larger-sized CMs from high energy synthesis cluster. Of note, we found the expression of Cytochrome c oxidase subunit 7B (Cox7B), a subunit of Complex IV in ETC was positively correlated with CMs size. Further, after assessing Cox7B expression in HCM patients, we speculated that Cox7B was compensatory up-regulated at early-stage but down-regulated at end-stage of HCM. To test the hypothesis that Cox7B might play a cardioprotective role in the early-stage of HCM, we used adeno associated virus 9 (AAV9) to mediate the expression of Cox7B in pressure overload-induced mice. Mice in vivo data supported that knockdown of Cox7B would accelerate heart failure progression and Cox7B overexpression could restore partial cardiac function in hypertrophy. Overall design: Primary cardiocytes were isolated from human heart of HCM patients. We applied single-cell tagged reverse transcription (STRT-seq) approach and obtained 338 CM transcriptome.