PgmNr M306: Muscle fiber signaling scales the myogenic stem cell pool.

Authors:
Christoph Lepper Lepper 1 ; Sheryl Southard 1 ; Ju-Ryoung Kim 2 ; Richard Tsika 2


Institutes
1) Carnegie Institution for Science, Baltimore, MD; 2) University of Missouri, Columbia, MO.


Abstract:

When unperturbed, quiescent somatic stem cells are poised to affect immediate tissue restoration upon trauma. Yet, little is known regarding the mechanistic basis controlling initial and homeostatic 'scaling' of adult stem cell pool sizes relative to their target tissues for effective regeneration. Here, we show that transgenic TEAD1 (TgTg(Ckm-Tead1)#Tsik)-expressing skeletal muscle features a dramatic hyperplasia of muscle stem cells (i.e. the satellite cells, SCs) but surprisingly without affecting muscle tissue size. Such super-numeral SCs attain a 'normal' quiescent state, accelerate regeneration, and maintain regenerative capacity over several injury-induced regeneration bouts. In dystrophic muscle, the TEAD1 transgene also ameliorated the pathology. We further demonstrate that hyperplastic SCs accumulate non-cell-autonomously via signal(s) from the TEAD1- expressing myofiber, suggesting that myofiber-specific TEAD1 overexpression activates a physiological signaling pathway(s) that determine initial and homeostatic SC pool size. We propose that TEAD1 and its downstream effectors are medically relevant targets for enhancing muscle regeneration.