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We are pleased to welcome Shahragim Tajbakhsh , from the Institut Pasteur, who has been invited by Team Mounier.

He will give a seminar entitled “ Dynamics of muscle stem/niche cells in regeneration and disease ” on Thursday, Novembrer 5th at 11:00 a.m.

The seminar will take place in Amphi Physique (ground floor), Faculty of Medicine Lyon-Est Rockefeller.

Abstract

Muscle stem cells (MuSCs) are governed by intrinsic and extrinsic pathways that control quiescence, activation and lineage progression. Using intravital and ex vivo live imaging in the mdx mouse model of Duchenne Muscular Dystrophy (DMD), we showed that dystrophic MuSCs have impaired migration and differentiate precociously through unbalanced symmetric divisions driven by p38 and PI3K signalling. Cross-grafting revealed that fate decisions are fibre-independent, whereas migration is dictated by the myofibre niche, establishing DMD as a MuSC disease with niche dysfunction (1).

We showed previously that distinct metabolic states govern MuSC fate (2). Using respiratory influenza infection and non-metastatic tumour-induced cachexia, we showed that MuSCs in uninjured muscles adopt a novel quiescent state (GPath) characterised by reduced cell size, suppressed oxidative phosphorylation and diminished mTORC1 activity. Despite erosion of canonical quiescence regulators, cell-cycle entry is restrained before S-phase, consistent with insufficient mTORC1-dependent anabolic drive for G1 commitment (3).

Muscles also differ in resilience. Extraocular muscle (EOM) stem cells have greater proliferative capacity and a distinct Foxc1-centred identity (4). Under identical tumour burden, EOMs resist wasting while limb muscles atrophy. EOM stem cells maintain higher lysosomal content and autophagic flux, preserving the compartment for mTORC1 recruitment, and upregulate IGF1 under cachexia; IGF1R inhibition derepresses atrogene induction in the protected EOM (5). Together, these findings identify the lysosomal–mTORC1 axis as a convergent node governing MuSC activation competence and tissue resilience.

References

1) Sarde L et al. (2026). Nat Commun 17:1769.

2) Pala F et al. (2018). J Cell Sci 131(14).

3) Gayraud-Morel B, Di Girolamo D et al. Systemic pathologies induce a distinct quiescent state in tissue-resident stem cells. In revision.

4) Di Girolamo D, Benavente-Diaz M et al., (2024). Development 151(4).

5) Murolo M, Duarte P et al. A stem cell-derived IGF niche program protects muscles from cancer cachexia. In revision.

Please feel free to forward this announcement to other institutes and colleagues who may be interested.

We look forward to seeing you there!