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

项目摘要 在组织修复期间，许多干细胞群体经历了从静止状态到动态表型的变化。 变为激活状态。在肌肉干细胞(MuSCs)中，这种动态激活过程是有效的 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不清楚。我们已经产生了单个细胞 这些分析使我们能够研究成年和老年MuSCs在激活过程中的状态转变。这些结果 支持老年干细胞表型的概念性观点，认为它是病理稳定状态和 细胞状态动力学方面的缺陷。这为我们提供了确定使MUSC恢复活力的因素的机会 在衰老过程中发挥作用。在这个项目中，我们将研究生理性返老还童干预在 MUSC的异质性和活化态转变。了解返老还童干预如何控制 MUSC的激活反应是有效治疗不断扩大的老年人口的关键。

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.