Biology subjects

Barruet, E.

Publications and source records attributed to Barruet, E..

5 recordsLinked to original sources

bioRxiv2025

Control of Quiescence and Activation of Human Muscle Stem Cells by Cytokines

Skeletal muscle homeostasis and repair depend on the activation of tissue resident stem cells called satellite cells. To understand the early molecular basis of human satellite cell activation, epigenomics, transcriptomics and protein analysis were performed in quiescent and activated human satellite cells. Cytokine signaling pathways were enriched in stimulated human satellite cells revealing a high cytokine enrichment, including CCL2, CCL20, CXCL8, IL-6, TNFRSF12A, ILR1, CSF-1 and FGF2. Functional roles of these observed changes are supported by in vivo experiments showing that chemokine inhibitors increase engraftment and regeneration capacity of human satellite cells xenotransplants. Cytokines, chemokines and associated signaling pathways in the early stages of human satellite cell activation may underlie disparate muscle responses in neuromuscular inflammatory and degenerative disorders and consequently are potential entry points for clinical applications towards muscle repair.

cell biology↗

bioRxiv2023

Patterning and folding of intestinal villi by active mesenchymal dewetting

Tissue folding generates structural motifs critical to organ function. In the intestine, bending of a flat epithelium into a periodic pattern of folds gives rise to villi, the numerous finger-like protrusions that are essential for nutrient absorption. However, the molecular and mechanical mechanisms driving the initiation and morphogenesis of villi remain a matter of debate. Here, we identify an active mechanical mechanism that simultaneously patterns and folds intestinal villi. We find that PDGFRA+ subepithelial mesenchymal cells generate myosin II-dependent forces sufficient to produce patterned curvature in neighboring tissue interfaces. At the cell-level, this occurs through a process dependent upon matrix metalloproteinase-mediated tissue fluidization and altered cell-ECM adhesion. By combining computational models with in vivo experiments, we reveal these cellular features manifest at the tissue-level as differences in interfacial tensions that promote mesenchymal aggregation and interface bending through a process analogous to the active de-wetting of a thin liquid film.

developmental biology↗

bioRxiv2022

Loss of transcriptional heterogeneity in aged human muscle stem cells

Age-related loss of muscle mass and function negatively impacts healthspan and lifespan. Satellite cells function as muscle stem cells in muscle maintenance and regeneration by self-renewal, activation, proliferation and differentiation. These processes are perturbed in aging at the stem cell population level, contributing to muscle loss. However, how representation of subpopulations within the human satellite cell pool change during aging remains poorly understood. We previously reported a comprehensive baseline of human satellite cell (Hu-MuSCs) transcriptional activity in muscle homeostasis describing functional heterogenous human satellite cell subpopulations such as CAV1+ Hu-MUSCs (Barruet et al., 2020). Here, we sequenced additional satellite cells from new healthy donors and performed extended transcriptomic analyses with regard to aging. We found an age-related loss of global transcriptomic heterogeneity and identified new markers (CAV1, CXCL14, GPX3) along with previously described ones (FN1, ITGB1, SPRY1) that are altered during aging in human satellite cells. These findings describe new transcriptomic changes that occur during aging in human satellite cells and provide a foundation for understanding functional impact.

cell biology↗

bioRxiv2021

ACVR1R206H increases osteogenic/ECM gene expression and impairs myofiber formation in human skeletal muscle stem cells

Abnormalities in skeletal muscle repair lead to poor function and complications such as scarring or heterotopic ossification (HO). Here, we use fibrodysplasia ossificans progressiva (FOP), a disease of progressive HO caused by ACVR1R206H (Activin receptor type-1 receptor) mutation, to elucidate how ACVR1 affects skeletal muscle repair. Rare and unique primary FOP human muscle stem cells (Hu-MuSCs) isolated from cadaveric skeletal muscle demonstrated increased ECM marker expression, and showed skeletal muscle-specific impaired engraftment and regeneration ability. Human induced pluripotent stem cell (iPSC)-derived muscle stem/progenitor cells (iMPCs) Single cell transcriptome analyses from FOP also revealed unusually increased ECM and osteogenic marker expression compared to control iMPCs. These results show that iMPCs can recapitulate many aspects of Hu-MuSCs for detailed in vitro study, that ACVR1 is a key regulator of Hu-MuSC function and skeletal muscle repair; and that ACVR1 activation in iMPCs or Hu-MuSCs contributes to HO by changing the local tissue environment.

cell biology↗

bioRxiv2020

β-catenin Signaling Regulates Cell Fate Decisions at the Transition Zone of the Chondro-Osseous Junction During Fracture Healing

Chondrocytes within the fracture callus transform into osteoblasts during bone regeneration, but the molecular mechanisms regulating this process are unknown. Wnt ligands are expressed within the fracture callus, and hypertrophic chondrocytes undergoing transformation to osteoblasts exhibit nuclear localization of {beta}-catenin, indicating active Wnt signaling in these cells. Here, we show that conditional knock out (cKO) of {beta}-catenin in chondrocytes inhibits the transformation of chondrocytes to osteoblasts, while stabilization of {beta}-catenin in chondrocytes accelerates this process. After cKO, chondrocyte-derived cells were located in the bone marrow cavity and upon re-fracture formed cartilage. Lineage tracing in wild type mice revealed that in addition to osteoblasts, chondrocytes give rise to stem cells that contribute to repair of subsequent fractures. These data indicate that Wnt signaling directs cell fate choices of chondrocytes during fracture healing by stimulating transformation of chondrocytes to osteoblasts, and provide a framework for developing Wnt-therapies to stimulate repair.

developmental biology↗