Biology subjects

Vissing, K.

Publications and source records attributed to Vissing, K..

3 recordsLinked to original sources

bioRxiv2026

Fibro-adipogenic Progenitor and Macrophage Remodeling of the Aging Skeletal Muscle Niche During Exercise-Induced Hypertrophy

Fibro-adipogenic progenitors (FAPs) have emerged as central regulators of the skeletal muscle homeostasis and the muscle microenvironment. However, the role of FAPs in the context of exercise-induced muscle hypertrophy remains largely unexplored. Here, we utilized six weeks of blood flow restricted resistance exercise (BFRRE) to study cellular adaptations within the muscle microenvironment accompanying muscle hypertrophy in healthy older individuals. Using flow cytometry, we characterized global changes of key cell populations within the skeletal muscle microenvironment, including FAPs, muscle stem cells (MuSCs), and immune cells. BFRRE induced significant enlargement of both FAPs and MuSCs, consistent with cellular adaptation to exercise. Notably, exercise shifted the FAP pool toward an increased predominance of the CD90high FAP phenotype, without altering total FAP abundance. In addition to matrix and collagen-related genes, transcriptional analysis of genes associated with secretory proteins revealed enrichment of promyogenic factors in CD90high versus CD90low FAPs. Conditioned media experiments of freshly isolated FAPs demonstrated that CD90high FAPs promote myotube growth in vitro compared to CD90low counterparts, suggesting that this phenotypic shift may facilitate muscle hypertrophy. In parallel, BFRRE increased the proportion of pro-inflammatory (CD11c+) macrophages within the skeletal muscle niche, highlighting a dynamic immune response during adaptation. Finally, we show identified possible link between pro-inflammatory macrophages and FAPs, as TNF markedly reduced the proliferation of human primary FAPs ex vivo, suggesting that macrophage-derived signals may attenuate excessive FAP expansion during tissue remodelling. Together, these findings provide new insight into how the remodelling of the cellular niche may support muscle hypertrophy in response to exercise. The coordinated expansion and phenotypic remodeling of FAP and immune cell populations may represent an important mechanism through which exercise supports hypertrophy in older individuals.

cell biology↗

bioRxiv2026

The muscle atrophic phenotype of MuSK myasthenia gravis: Insights from a preclinical rat model

Myasthenia gravis with muscle-specific kinase antibodies (MuSK-MG) is an autoimmune disorder marked by neuromuscular junction (NMJ) disruption and selective muscle atrophy, yet its intrinsic myocellular mechanisms remain unclear. Using a rat model generated by active immunization with the N-terminal MuSK60 peptide, we characterized muscle pathology, NMJ morphology, and whole-muscle proteome remodeling across anatomically distinct skeletal muscles. Anti-MuSK rats developed seropositivity, body-mass loss, fragmented and denervated NMJs, and pronounced atrophy restricted to slow-twitch/type I fibers, particularly in the soleus muscle. Quantitative proteomics identified extensive muscle-specific alterations, most prominent in soleus, with fewer in diaphragm and sternohyoideus. Gene set enrichment analysis revealed coordinated downregulation of mitochondrial, ribosomal, and myosin-complex proteins in soleus, partial mitochondrial involvement in diaphragm, and compensatory upregulation of translational and proteasomal pathways in diaphragm. Correlation analysis linked soleus mass loss to elevated abundance of ubiquitin-proteasome and calcium-handling proteins, implicating proteolytic and bioenergetic stress mechanisms. The consistent upregulation of NCAM1 and MUSTN1 suggests generalized myocellular responses to MuSK dysfunction. Together, these data demonstrate that MuSK autoimmunity elicits fiber-type-selective atrophy and profound proteome remodeling beyond NMJ impairment, highlighting disrupted mitochondrial and translational homeostasis as central features of the MuSK-MG muscle phenotype.

molecular biology↗

bioRxiv2024

CD90 identifies distinct fractions of muscle stem cells with different modalities of activation and quiescence maintenance

Stem cell transition from quiescence to activation is crucial to guarantee productive tissue regeneration. Here we show that CD90 diversifies quiescent muscle stem cells (MuSCs) in murine and human muscle into two subpopulations differing in the kinetics of activation, CD90+ve MuSCs exhibiting a faster exit quiescence and predominating the initial phases of regeneration compared to CD90-ve MuSCs. In the absence of injury, the CD90+ve fraction is primed toward activation through an active CD90-AMPK axis but is maintained in quiescence through signals from the extracellular matrix. Our studies show that Collagen VI, which is preferentially expressed by CD90+ve MuSCs, binds to the Calcitonin receptor and plays a role in this context. Moreover, while the number of CD90+ve and CD90-ve subpopulations is similar in healthy muscles, the CD90-ve fraction predominates in the muscles of murine models of Duchenne and Ullrich congenital muscular dystrophies. These findings provide novel insights into the mechanistic determinants of MuSCs functional heterogeneity and have implications for understanding the stimulation of repair in dystrophic muscle.

cell biology↗