Beyond myoblasts: DUX4 alters the differentiation landscape and promotes a pro-fibrotic phenotype in mesenchymal stromal cells
Abstract
Facioscapulohumeral muscular dystrophy (FSHD) is caused by aberrant expression of the transcription factor DUX4 in skeletal muscle, leading to progressive muscle degeneration and pathological remodelling of the muscle microenvironment. Although the effects of DUX4 in myogenic cells have been extensively investigated, its potential impact on mesenchymal stromal cells (MSCs), which contribute to tissue homeostasis and regeneration, remains poorly understood. Here, we investigated the consequences of ectopic DUX4 expression in human MSCs and assessed their differentiation potential and transcriptional phenotype. DUX4expressing MSCs acquired selected features of the myogenic phenotype, including expression of muscle-associated markers and formation of myotube-like structures, although their myogenic differentiation and fusion capacity remained markedly lower than those of bona fide myoblasts. In parallel, DUX4 expression substantially altered MSC lineage potential, reducing adipogenic and osteogenic differentiation. Transcriptomic and functional analyses further revealed prominent activation of extracellular matrix (ECM)-associated and pro-fibrotic programmes, together with increased oxidative stress. These findings indicate that DUX4 profoundly alters the differentiation landscape of MSCs, inducing a complex cell state characterised by partial activation of muscle-associated programmes and a prominent profibrotic/ECM-remodelling phenotype. Our results suggest that DUX4 may influence not only myogenic cells but also mesenchymal populations within the FSHD muscle microenvironment.
Related
- Curcumin promotes osteogenic differentiation of bone marrow mesenchymal stem cells via the miR-206/Hdac4 signaling axis
- Circ_0018814 promotes the osteogenic differentiation of mesenchymal stem cells in ankylosing spondylitis by regulating the miR-944/KLF4 axis
- miR-191 affects skeletal muscle differentiation by regulating Wwp1 in mouse myoblasts
- RBFOX2 Autoregulation Promotes Cardiomyocyte Transcriptome Maturation and Differentiation
- Recent Advances in Neuronal-like Differentiation of Mesenchymal Stem/Stromal Cells
BibTeX
@article{serbina2026beyond,
title = {{Beyond myoblasts: DUX4 alters the differentiation landscape and promotes a pro-fibrotic phenotype in mesenchymal stromal cells}},
author = {Olesya Serbina and Anna Schwager and Ekaterina Kiseleva and Erdem Dashinimaev and Ekaterina Vorotelyak and Yegor Vassetzky},
journal = {Cell Communication and Signaling},
year = {2026},
month = aug,
doi = {10.1186/s12964-026-03162-x},
url = {https://hal.science/hal-05760293v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Beyond myoblasts: DUX4 alters the differentiation landscape and promotes a pro-fibrotic phenotype in mesenchymal stromal cells
AU - Olesya Serbina
AU - Anna Schwager
AU - Ekaterina Kiseleva
AU - Erdem Dashinimaev
AU - Ekaterina Vorotelyak
AU - Yegor Vassetzky
PY - 2026
DA - 2026/08/21
JO - Cell Communication and Signaling
DO - 10.1186/s12964-026-03162-x
UR - https://hal.science/hal-05760293v1
AB - Facioscapulohumeral muscular dystrophy (FSHD) is caused by aberrant expression of the transcription factor DUX4 in skeletal muscle, leading to progressive muscle degeneration and pathological remodelling of the muscle microenvironment. Although the effects of DUX4 in myogenic cells have been extensively investigated, its potential impact on mesenchymal stromal cells (MSCs), which contribute to tissue homeostasis and regeneration, remains poorly understood. Here, we investigated the consequences of ectopic DUX4 expression in human MSCs and assessed their differentiation potential and transcriptional phenotype. DUX4expressing MSCs acquired selected features of the myogenic phenotype, including expression of muscle-associated markers and formation of myotube-like structures, although their myogenic differentiation and fusion capacity remained markedly lower than those of bona fide myoblasts. In parallel, DUX4 expression substantially altered MSC lineage potential, reducing adipogenic and osteogenic differentiation. Transcriptomic and functional analyses further revealed prominent activation of extracellular matrix (ECM)-associated and pro-fibrotic programmes, together with increased oxidative stress. These findings indicate that DUX4 profoundly alters the differentiation landscape of MSCs, inducing a complex cell state characterised by partial activation of muscle-associated programmes and a prominent profibrotic/ECM-remodelling phenotype. Our results suggest that DUX4 may influence not only myogenic cells but also mesenchymal populations within the FSHD muscle microenvironment.
SN - 1478-811X
ER -