Aging induces aberrant state transition kinetics in murine muscle stem cells

• DOI: 10.1242/dev.183855
• Publication Date: 2020-03-20T19:15:32Z
• Authors: Jacob C. Kimmel; Ara B. Hwang; Annarita Scaramozza; Wallace F. Marshall; Andrew S. Brack
• Keywords: Male; 0303 health sciences; Stem Cells; Stem Cells and Regeneration; Immunohistochemistry; Time-Lapse Imaging; Mice, Inbred C57BL; Kinetics; Mice; 03 medical and health sciences; Animals; RNA-Seq; Muscle, Skeletal; Cells, Cultured; Cellular Senescence

Murine muscle stem cells (MuSCs) experience a transition from quiescence to activation that is required for regeneration, but it remains unknown if the trajectory and dynamics of change with age. Here, we use timelapse imaging single cell RNA-seq measure trajectories rates in young aged MuSCs. We find conserved cells, develop effective machine learning classifiers Using behavior analysis RNA velocity, kinetics are delayed MuSCs, suggesting changes may contribute impaired function Intriguingly, also appears be random walk like process, frequent reversals, rather than continuous, linear progression. These results support view phenotype as combination differences location stable states between them.