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

单细胞激活动力学作为老年 MuSC 功能障碍的预测因子和调节因子。

• 批准号: 9756173
• 负责人: Andrew S Brack
• 金额: $ 26.86万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-15 至 2021-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9756173
• 关键词: Adult; Aging; Back; Behavior; Behavior Therapy; Behavioral; Behavioral Assay; Biological Assay; Biological Markers; Caloric Restriction; Cell Aging; Cell physiology; Cells; Cellular Assay; Complement; Data; Development; Disease; Exercise; Exploratory/Developmental Grant; Exposure to; Fasting; Functional disorder; Future; Genetic Transcription; Heterogeneity; Intermittent fasting; Intervention; Investigation; Kinetics; Lead; Machine Learning; Maps; Methods; Molecular; Muscle satellite cell; Muscular Atrophy; Nature; Parabiosis; Pathologic; Phenotype; Physiological; Plasma; Process; Proxy; RNA; Rejuvenation; Research; Role; Series; Skeletal Muscle; Stem cells; Time; Tissues; aged; aging population; base; biomarker panel; cell age; cell behavior; effective therapy; falls; genetic variant; improved; muscle aging; novel; regenerative; response; satellite cell; single-cell RNA sequencing; stem cell population; tissue regeneration; tissue repair; tool; transcriptome; transcriptomics

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.

项目总结