肌肉干细胞在激活和增殖过程中存在异质性，即存在对称分裂和不对称分裂的亚群，以实现自我更新和分化成为新的肌肉组织。该过程涉及基因调控网络的转录激活和转录抑制，伴随着染色质开放性的动态变化。然而受限于细胞数量有限，肌肉干细胞激活和增殖过程中的基因网络和细胞异质性，以及表观遗传调控机制仍然不完全清楚。申请人前期研究建立了单细胞RNA和ATAC测序技术和数据分析方法，并用于绘制心脏早期发育细胞图谱。此外，申请人使用ATAC测序研究发现，肌肉干细胞从静息进入激活状态发生了显著的染色质重塑。基于前期建立的技术平台和研究成果，本项目将描绘肌肉干细胞在静息和激活状态下的单细胞转录组和单细胞染色质开放性图景，揭示其异质性，为干细胞不对称分裂模型和肌肉再生医学提供理论支撑。

Muscle stem cells are heterogeneous during activation and proliferation. The symmetric and asymmetric divisions of muscle stem cells are pivotal to self-renewal and regeneration of muscle tissue upon injury. This process involves transcriptional activation and transcriptional repression of the gene regulatory network, accompanying by chromatin accessibility dynamics. However, due to limited cell numbers, the gene regulatory network and cellular heterogeneity during muscle stem cell activation and proliferation, as well as epigenetic landscape dynamics remain to be elucidated. The applicant has established robust single-cell RNA and ATAC sequencing techniques and data analysis tools, which have been used to depict cell atlas of mouse early heart. In addition, using bulk ATAC-seq, the applicant found that quiescent muscle stem cells undergo significant chromatin remodeling upon activation and proliferation. Based on the techniques previously established and our preliminary results, this project will depict the single-cell transcriptome and single-cell chromatin accessibility landscape of muscle stem cells in quiescent, and activated states, and decipher the molecular mechanisms of a-/symmetric cell division. We expect our study will reveal muscle stem cell heterogeneity thereby benefitting muscle regenerative medicine.