Decoding the transcriptome of muscular dystrophy using single-nucleus RNA sequencing

Muscular dystrophy is a group of diseases that cause progressive weakness and degeneration of the skeletal muscles that control movement. Lacking polymerase I transcription release factor (PTRF, also known as Cavin1), an essential caveolae component, causes a secondary deficiency of caveolins resulting in muscular dystrophy. Because skeletal muscle is a heterogeneous tissue composed of different metabolic muscle fiber (myofibers) and mononuclear cells, the transcriptome responses of these myofibers and mononuclear cell to muscular dystrophy caused by PTRF deletion has not been explored. Here, we create muscular dystrophy mice caused by the deletion of PTRF gene and apply single-nucleus RNA sequencing (snRNA-seq) to unveil transcriptional changes in the skeletal muscle of mice with muscular dystrophy at single-nucleus resolution. We analyzed quadriceps muscles from 3-month-old WT and PTRF KO mice using single-nucleus sequencing.肌营养不良症（Muscular dystrophy）是一类可导致支配运动的骨骼肌进行性无力与变性的疾病。聚合酶I转录释放因子（polymerase I transcription release factor，简称PTRF，又名Cavin1）作为胞膜窖的核心组成成分，其缺失会引发窖蛋白继发性缺乏，进而导致肌营养不良症。由于骨骼肌是由不同代谢类型的肌纤维（myofibers）与单核细胞共同构成的异质性组织，目前尚未有研究探究肌纤维与单核细胞在PTRF缺失引发的肌营养不良症中的转录组应答反应。本研究通过敲除PTRF基因构建肌营养不良症小鼠模型，并利用单细胞核RNA测序（single-nucleus RNA sequencing, snRNA-seq）在单细胞核分辨率下解析患肌营养不良症小鼠骨骼肌的转录组变化。本研究采用单细胞核测序技术，对3月龄野生型（wild type, WT）与PTRF基因敲除（knockout, KO）小鼠的股四头肌进行了分析。