Biology subjects

Zvick, J.

Publications and source records attributed to Zvick, J..

2 recordsLinked to original sources

bioRxiv2023

Interspecies generation of functional muscle stem cells

Satellite cells, the stem cells of skeletal muscle tissue, hold a prodigious regeneration capacity. However, low satellite cell yield from autologous or donor-derived muscles precludes adoption of satellite cell transplantation for the treatment of muscle diseases including Duchenne muscular dystrophy (DMD). To address this limitation, here we investigated whether sufficient quantity of satellite cells can be produced in allogeneic or xenogeneic animal hosts. First, we report on exclusive satellite cell production in intraspecies mouse chimeras by injection of CRISPR/Cas9-corrected DMD-induced pluripotent stem cells (iPSCs) into blastocysts carrying an ablation system of host Pax7+ satellite cells. Additionally, injection of genetically-corrected DMD-iPSCs into rat blastocysts produced interspecies rat-mouse chimeras harboring mouse muscle stem cells that efficiently restored dystrophin expression in DMD mice. This study thus provides a proof-of-principle for the generation of therapeutically-competent stem cells between divergent species, raising the possibility of procuring human stem cells in large animals for regenerative medicine purposes.

cell biology↗

bioRxiv2020

Exercise promotes satellite cell contribution to myofibers in a load-dependent manner

Satellite cells (SCs) are required for muscle repair following injury and are involved in muscle remodeling upon muscular contractions. Exercise stimulates SC accumulation and myonuclear accretion. To what extent exercise training at different mechanical loads drive SC contribution to myonuclei however is unknown. By performing SC fate tracing experiments, we show that 8-weeks of voluntary wheel running increased SC contribution to myonuclei in mouse plantar flexor muscles in a load-dependent but fiber type-independent manner. Increased SC fusion however was not exclusively linked to muscle hypertrophy as wheel running without external load substantially increased SC fusion in the absence of fiber hypertrophy. Due to nuclear propagation, nuclear fluorescent fate tracing mouse models were inadequate to quantify SC contribution to myonuclei. Ultimately, by performing fate tracing at the DNA level, we show that SC contribution mirrors myonuclear accretion during exercise. Collectively, these findings provide direct evidence that mechanical load during exercise independently promotes SC contribution to existing myofibers.

cell biology↗