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The differentiation of dystrophic stem cells relied on dual p38–PI3K signalling, an unrecognised synergy not seen in healthy cells which depended solely on p38.

For mechanistic studies we developed an in vitro live imaging assay with isolated stem cells.

Stem cell fate decisions were cell-autonomous, while their migration behaviour was largely determined by the healthy vs dystrophic muscle fibre niches.

To explore the contribution of autonomous vs niche-driven cues, we set up a niche switching assay between healthy and dystrophic stem cells and muscle fibres.

(YFP-labelled dystrophic stem cell grafted to a healthy fibre here)

Ex vivo dystrophic stem cells indeed showed altered migration and precocious differentiation, through imbalanced symmetric divisions.

We developed an ex vivo live imaging assay with stem cells within their muscle fibre niche to recapitulate the in vivo phenotypes and allow for perturbation studies.

Using in vivo live imaging, we showed that dystrophic stem cells have impaired migration kinetics and precocious differentiation.