Metabolic Heterogeneity of Muscle Stem Cells is Controlled by the Myofiber Niche
- 1INSERM U1055 - University Grenoble Alpes, Laboratory of Fundamental and Applied Bioenergetics
Abstract
Metabolic pathways support biomass synthesis and provide substrates for epigenetic modifications of histones and DNA. These findings are particularly relevant for adult stem cells, where metabolic changes significantly impact functional behavior. However, assessing the metabolism of these cells in their native microenvironment is challenging as this typically necessitates dissociation prior to metabolic analysis. In this study, we focus on muscle stem cells (MuSCs) and show that removing these cells from the niche significantly alters their metabolic profile. To overcome this issue, we developed a novel enzymatic staining method for in situ metabolic profiling at a single-cell resolution. This approach reveals unexpected metabolic heterogeneity of MuSCs, identifying oxidative and glycolytic subsets, and demonstrates that their metabolism is directly modulated by adjacent myofibers. Accordingly, perturbing myofiber metabolism remodels the MuSC niche and drives metabolic adaptation in MuSCs. Finally, we define the kinetics by which myofiber-dependent metabolic regulation of MuSCs is re-established during muscle regeneration, thereby revealing how niche-imposed metabolic cues shape stem cell identity in vivo.
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BibTeX
@misc{chabert2026metabolic,
title = {{Metabolic Heterogeneity of Muscle Stem Cells is Controlled by the Myofiber Niche}},
author = {C. Chabert and M. Quetin and L. Neff and A. Bonavoglia and O. M. Dorchies and P. Mourikis and F. Relaix and M. Gervais and A. Prola},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.04.749367},
url = {https://www.biorxiv.org/content/10.64898/2026.09.04.749367v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Metabolic Heterogeneity of Muscle Stem Cells is Controlled by the Myofiber Niche
AU - C. Chabert
AU - M. Quetin
AU - L. Neff
AU - A. Bonavoglia
AU - O. M. Dorchies
AU - P. Mourikis
AU - F. Relaix
AU - M. Gervais
AU - A. Prola
PY - 2026
DA - 2026/09/04
PB - bioRxiv
DO - 10.64898/2026.09.04.749367
UR - https://www.biorxiv.org/content/10.64898/2026.09.04.749367v1
AB - Metabolic pathways support biomass synthesis and provide substrates for epigenetic modifications of histones and DNA. These findings are particularly relevant for adult stem cells, where metabolic changes significantly impact functional behavior. However, assessing the metabolism of these cells in their native microenvironment is challenging as this typically necessitates dissociation prior to metabolic analysis. In this study, we focus on muscle stem cells (MuSCs) and show that removing these cells from the niche significantly alters their metabolic profile. To overcome this issue, we developed a novel enzymatic staining method for in situ metabolic profiling at a single-cell resolution. This approach reveals unexpected metabolic heterogeneity of MuSCs, identifying oxidative and glycolytic subsets, and demonstrates that their metabolism is directly modulated by adjacent myofibers. Accordingly, perturbing myofiber metabolism remodels the MuSC niche and drives metabolic adaptation in MuSCs. Finally, we define the kinetics by which myofiber-dependent metabolic regulation of MuSCs is re-established during muscle regeneration, thereby revealing how niche-imposed metabolic cues shape stem cell identity in vivo.
ER -