Reprogramming of Cis-regulatory networks during skeletal muscle atrophy [snATAC-seq]. Reprogramming of Cis-regulatory networks during skeletal muscle atrophy [snATAC-seq]

Current atlas of regulatory sequences controlling skeletal muscle atrophy are still incomplete and lack cell type resolution. We applied single-cell chromatin accessibility assays (snATAC) to normal and denervated skeletal muscle from mice. We integrated these snATAC datasets with our single-nucleus RNA-sequence dataset to reveal the status of open chromatin. Using these datasets, we delineated chromatin accessibility maps in both normal and atrophic muscles and identified cis-regulatory elements (CREs) in all type of cell in skeletal muscle that may regulating muscle protein metabolism, energy metabolism and transcription activities, thus, provided a rich resource for understanding gene regulatory programs in skeletal muscle and related disorders. Overall design: Single-nucleus ATAC-seq in normal and denervated mice.

目前调控骨骼肌萎缩的调控序列图谱仍不完善，且缺乏细胞类型分辨率。我们对小鼠正常及去神经支配的骨骼肌开展了单细胞染色质开放性检测（single-cell chromatin accessibility assays, snATAC），并将这些snATAC数据集与单核RNA测序数据集进行整合以解析染色质开放状态。利用上述数据集，我们绘制了正常及萎缩骨骼肌的染色质开放性图谱，鉴定出骨骼肌所有细胞类型中可调控肌肉蛋白质代谢、能量代谢及转录活性的顺式调控元件（cis-regulatory elements, CREs），进而为解析骨骼肌的基因调控程序及相关疾病提供了丰富的研究资源。实验整体设计：针对正常及去神经支配小鼠开展单核ATAC测序。