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.

Public Health Relevance

Satellite cells or Muscle stem cells (MuSCs) are heterogeneous at the molecular and function level. Aging leads to a loss of MuSC function through a delay in activation at the level of molecular and behavioral kinetics. We have developed an exciting and novel project that will identify rejuvenation interventions that activation state transitions at the single cell level.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AG063416-02
Application #
9891934
Study Section
Cellular Mechanisms in Aging and Development Study Section (CMAD)
Program Officer
Williams, John
Project Start
2019-02-01
Project End
2021-01-31
Budget Start
2020-03-01
Budget End
2021-01-31
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Orthopedics
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118