# Impaired stem cell migration and divisions in Duchenne muscular dystrophy revealed by live imaging

## TL;DR

This study uses live imaging to show that muscle stem cells in Duchenne muscular dystrophy have impaired migration and abnormal division patterns.

## Contribution

The study introduces live imaging of dystrophic muscle stem cells in vivo and ex vivo, revealing novel insights into their dynamic behavior and signaling pathways.

## Key findings

- Dystrophic muscle stem cells show impaired migration and unbalanced symmetric divisions.
- p38 and PI3K pathways drive precocious differentiation in dystrophic stem cells.
- Migration behavior is influenced by the myofibre niche, while fate decisions are fibre-independent.

## Abstract

Dysregulation of stem cell properties is a hallmark of many pathologies, but the dynamic behaviour of stem cells in their microenvironment during disease progression remains poorly understood. Using the mdx mouse model of Duchenne Muscular Dystrophy, we developed innovative live imaging of muscle stem cells (MuSCs) in vivo, and ex vivo on isolated myofibres. We show that mdx MuSCs have impaired migration and precocious differentiation through unbalanced symmetric divisions, driven by p38 and PI3K signalling pathways, in contrast to the p38-only dependence of healthy MuSCs. Cross-grafting shows that MuSC fate decisions are governed by fibre-independent cues, whereas their migration behaviour is determined by the myofibre niche. This study provides the first dynamic analysis of dystrophic MuSC properties in vivo, reconciling conflicting reports on their function. Our findings establish DMD as a MuSC disease with niche dysfunctions, offering strategies to restore stem cell functions for improved muscle regeneration.

Using live-imaging in vivo and ex vivo, Sarde et al. show that dystrophic muscle stem cells have precocious differentiation through symmetric divisions and impaired migration, with differential impact of the myofibre niche upon cross-transplantation.