Single cell activation dynamics as a predictor and regulator of aged MuSC dysfunction.

项目摘要 在组织修复过程中，许多干细胞群体从静止状态经历动态表型变化 到激活状态。在肌肉干细胞（MuSC）中，这种动态激活过程对于有效的细胞增殖至关重要。 组织再生尽管这些激活过程具有保守性，但干细胞的动力学 激活及其对疾病状态的贡献在很大程度上仍然未知。我们已经产生了单细胞 这些分析使我们能够研究成年和老年MuSC在激活过程中的状态转变。这些结果 支持衰老干细胞表型的概念观点，即衰老干细胞表型是病理稳态和 细胞状态动力学的缺陷。这为我们提供了一个机会，以确定振兴MuSC的因素 在老化过程中发挥作用。在这个项目中，我们将研究生理复壮干预的作用， MuSC异质性和激活状态转换。了解再生干预措施如何控制 MuSC激活反应对于不断扩大的老年人群的有效治疗至关重要。

Project Summary During tissue repair, many stem cell populations undergo a dynamic phenotypic change from a quiescent state to an activated state. In muscle stem cells (MuSCs), this dynamic activation process is essential for effective tissue regeneration. Despite the conserved nature of these activation processes, the dynamics of stem cell activation and their contribution to disease states remains largely unknown. We have generated single cell assays that allowed us to study state transitions of adult and aged MuSCs during activation. These results support a conceptual view of the aged stem cell phenotype as a combination of pathological steady-states and deficiencies in cell state dynamics. This provides us with the opportunity to identify factors that rejuvenate MuSC function during aging. In this project we will examine the role of physiological rejuvenation interventions on MuSC heterogeneity and activation state transitions. Understanding how rejuvenation interventions control MuSC activation response is critical for the effective treatment of the ever-expanding aged population.