Skeletal Muscle最新文献

{"title":"Klhl41b orchestrates sarcomere assembly and growth to drive skeletal muscle hypertrophy in vivo.","authors":"Hyewon Han, Grace R Tate, Janet Shi, Alfredo H Bongiorno, Arian Mansur, Jeffrey Widrick, Sehajpreet Gill, Esmat Karimi, Henk Granzier, Jeffrey R Moore, Vandana A Gupta","doi":"10.1186/s13395-026-00453-2","DOIUrl":"10.1186/s13395-026-00453-2","url":null,"abstract":"<p><strong>Background: </strong>Nemaline myopathy (NM) is a clinically and genetically heterogeneous disease caused by mutations in sarcomere-associated genes, with congenital forms representing the most severe end of the spectrum. Recessive mutations in KLHL41 underlie a severe congenital NM characterized by sarcomeric disorganization and impaired muscle growth. The in vivo mechanisms by which KLHL41 governs sarcomere assembly and growth remain poorly understood.</p><p><strong>Methods: </strong>We generated zebrafish models of KLHL41 deficiency by the CRISPR-Cas9 approach to examine the temporal and molecular basis of sarcomere assembly defects in NM. The phenotypic and physiological characterization of skeletal muscle defects was investigated by birefringence, spontaneous coiling, spontaneous swimming behavior, and force generation assays. Structural analyses by electron microscopy and immunofluorescence assessed myofibril organization and sarcomere structures across developmental time points. Quantitative proteomics and biochemical assays were performed to identify perturbations in sarcomeric proteins and associated molecular pathways.</p><p><strong>Results: </strong>We show that Klhl41b is essential for the formation and organization of sarcomeres, supporting both radial and longitudinal muscle growth. Loss of Klhl41b resulted in reduced sarcomere size, defective sarcomere assembly followed by progressive destabilization of sarcomeres, nemaline body formation, and reduced muscle function. Proteomic analysis in Klhl41b-deficient zebrafish revealed reduced abundance of the sarcomeric troponin complex proteins, altered abundance of components of the translational machinery, and increased abundance of components of atrophy-associated pathways.</p><p><strong>Conclusions: </strong>These data show that Klhl41b is required for sarcomere assembly and growth, and its deficiency drives a cascade of structural and molecular changes underlying skeletal muscle hypotrophy and NM pathology. These findings advance our understanding of disease mechanisms and may inform targeted therapeutic strategies to restore sarcomere integrity and muscle function.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":"16 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Duchenne muscular dystrophy: from gene to gene-ius therapies.","authors":"Antoine Muchir, Antonio Musaro, Jeffrey Chamberlain","doi":"10.1186/s13395-026-00439-0","DOIUrl":"10.1186/s13395-026-00439-0","url":null,"abstract":"<p><p>Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the dystrophin gene that result in the absence of functional dystrophin, leading to progressive muscle degeneration, loss of ambulation, respiratory failure, cardiomyopathy, and premature mortality. Despite advances in multidisciplinary supportive care, DMD remains an incurable disease associated with substantial physical, psychosocial, and economic burdens. The monogenic nature of DMD and its well-defined molecular pathogenesis have made it a prime target for the development of precision therapies aimed at restoring dystrophin expression or modifying disease progression. This review provides an overview of the genetic and molecular mechanisms underlying DMD, summarizes its clinical manifestations and natural history, and discusses current standards of care. It further examines recent advances in disease-modifying therapeutic strategies, including exon-skipping antisense oligonucleotides, nonsense mutation readthrough agents, adeno-associated virus (AAV)-mediated micro-dystrophin gene replacement, and emerging genome-editing technologies such as CRISPR/Cas9. The review also highlights the limitations of existing treatments, including mutation specificity, variable efficacy, immune-related challenges, and uncertainties regarding long-term durability and safety. Finally, it considers future directions in therapeutic development, emphasizing the need for combination approaches, improved delivery systems, and next-generation gene-editing platforms to achieve more effective and lasting clinical outcomes. Collectively, these advances represent a paradigm shift in DMD management and offer renewed hope for improving survival and quality of life for affected individuals.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":"16 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148907052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of a serum protein signature as monitoring biomarker for Duchenne muscular dystrophy in a long-term clinical trial with corticosteroids.","authors":"Chiara Degan, Rebecca A Tobin, Sharon I de Vries, Albert Jiménez-Requena, Amela Peco, Michela Guglieri, Jordi Diaz-Manera, Yuri E M van der Burgt, Bart J M van Vlijmen, Yetrib Hathout, Cristina Al-Khalili Szigyarto, Utkarsh J Dang, Roula Tsonaka, Pietro Spitali","doi":"10.1186/s13395-026-00437-2","DOIUrl":"10.1186/s13395-026-00437-2","url":null,"abstract":"<p><strong>Background: </strong>Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder for which monitoring biomarkers are urgently needed. We aimed to evaluate whether proteins in serum can accurately monitor patients' function within the duration of a clinical trial.</p><p><strong>Methods: </strong>In this study, we evaluated longitudinal serum proteins of DMD patients participating in the FOR-DMD clinical trial, comparing daily and intermittent corticosteroid regimens in boys aged 4-8 years at baseline. Using the aptamer-based protein platform SomaScan, we profiled 1500 proteins. Associations between protein levels and motor function outcomes, such as Rise from the Floor Velocity (RFV), 10-Meter Run/Walk Velocity (10MRWV), and North Star Ambulatory Assessment (NSAA), were assessed using linear mixed models. In particular, we explored whether patients with higher protein levels also tended to have better functional scores (across-patients analysis), and whether changes in protein levels within the same patient over time were linked to changes in their functional performance (within-patient analysis). Finally, penalized (lasso) mixed models were applied to evaluate the predictive function of the proteins. The prediction accuracy of the models (evaluated by optimism-corrected Root Mean Squared Error) was compared to that of a simpler model with only age and treatment as predictors.</p><p><strong>Results: </strong>Across-patients and within-patient analyses revealed consistent associations with three functional tests for a subset of proteins, notably RGMA, ART3, ANTXR2, and CFB. Multivariate models incorporating the proteins significantly associated with at least two tests, improved prediction accuracy by 12% for NSAA, and by 33-35% for RFV and 10MRWV. These models also revealed a subset of proteins that were consistently selected. Quantification of CFB, RGMA, ANTXR2, SERPINF1 and ATP5PF using SomaScan showed strong agreement with measurements obtained using orthogonal methods such as ELISA, MRM-MS and an in-house developed bead-based sandwich immunoassay.</p><p><strong>Conclusions: </strong>These findings support the utility of serum protein signatures as objective, quantitative tools for monitoring disease progression and treatment response in DMD during clinical visits and clinical trials.</p><p><strong>Trial registration: </strong>The FOR-DMD clinical trial was registered at ClinicalTrials.gov (registration no. NCT01603407). First submission: 03/04/2012.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13647910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NSAIDs trigger drug-specific response to exercise: a multi-omics systems biology analysis of a randomized crossover trial.","authors":"Brandon M Roberts, Alexander B Lawrence, Swapna Kannan, Alyssa V Geddis, Cara E Sczuroski, Jess A Gwin, Candace Moyler, Allison Hoke, Aarti Gautam, Jeffery S Staab, Ronald W Matheny, Rasha Hammamieh, Nabarun Chakraborty","doi":"10.1186/s13395-026-00435-4","DOIUrl":"10.1186/s13395-026-00435-4","url":null,"abstract":"<p><strong>Background: </strong>Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used by athletes and those who exercise, yet their influence on the molecular responses to exercise remains unclear. Prior studies have often focused on a limited set of molecular pathways, potentially overlooking broader regulator effects of NSAIDs on skeletal muscle signaling. Therefore, we conducted a systems biology study of skeletal muscle biopsies taken before and after exercise, in combination with NSAID consumption, using transcriptomics and metabolomics, to identify differentially enriched pathways and biofunctions.</p><p><strong>Methods: </strong>We conducted a randomized, counterbalanced, double-masked, crossover trial (NCT05512013) in which 12 healthy adults ingested ibuprofen (IBU, 800 mg), celecoxib (CEL, 200 mg), flurbiprofen (FLU, 100 mg), or placebo (PLA) before a 10 × 10 bout of plyometric exercise. Skeletal muscle biopsies were collected before NSAID consumption and three hours post-exercise. Whole transcriptome profiling was performed using RNA-seq, and the metabolomics profile was assessed via untargeted mass spectrometry. Differential expression analysis and pathway enrichment were used to evaluate NSAID-specific effects across biological domains.</p><p><strong>Results: </strong>FLU regulated the largest number of differentially expressed transcripts, followed by IBU and CEL. All NSAIDs activated immune-related gene networks and reversed exercise-induced lipid catabolism, with IBU enhancing adaptive immune signaling and CEL modulating both innate and adaptive pathways. Muscle remodeling pathways, including angiogenesis and cell migration, were activated across all NSAIDs, though cachexia-related genes were also upregulated. Interestingly, FLU uniquely upregulated transcripts involved in neuritogenesis.</p><p><strong>Conclusion: </strong>NSAIDs trigger drug-specific molecular responses in skeletal muscle post-exercise, affecting early recovery through changes in immune, metabolic, and neuronal signaling.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regenerative Index: a method to assess muscle regeneration in patients with Duchenne muscular dystrophy.","authors":"Johnathan K Smid, Charis A McPherson, Jacob G Monast, Shanti S S Rayagiri, Steven A Moore, Michael A Rudnicki","doi":"10.1186/s13395-026-00436-3","DOIUrl":"10.1186/s13395-026-00436-3","url":null,"abstract":"<p><strong>Background: </strong>Duchenne muscular dystrophy (DMD) is a devastating disease manifested in skeletal muscle by repetitious myonecrosis and regeneration. Because the regenerative process is closely linked to the cumulative severity of muscle damage, which is variably distributed within and between muscle groups, accurately quantifying muscle regeneration has remained a significant challenge.</p><p><strong>Methods: </strong>Myofibers are delineated by immunostaining for laminin, and subsequent image analysis employed to generate a masked outline precisely within each myofiber boundary. Morphometric parameters including minimal Feret's diameter, cross-sectional area, and circularity were measured for each myofiber. In addition, the number of Pax7-expressing satellite cells were quantified. To evaluate regenerative activity, newly formed myofibers were identified by immunostaining for expression of embryonic myosin heavy chain (eMHC). Necrotic myofibers were enumerated by immunofluorescent detection of immunoglobulin G (IgG) infiltration. The Regenerative Index (RI) was calculated as the number of regenerating (eMHC⁺) myofibers divided by the number of necrotic (IgG⁺) myofibers. Determination of RI was performed on muscle biopsies obtained from 10 boys with DMD and 3 age-matched non-DMD controls.</p><p><strong>Results: </strong>A trend toward an increasing minimal Feret's diameter, cross-sectional area and circularity was observed with increasing age in DMD boys, with circularity showing the strongest trend. Furthermore, compared to DMD boys 7- to 8-years old, the boys 9- to 11-years old had increased myofiber circularity. Pax7-expressing cells per myofiber were elevated in DMD boys compared to control boys of similar ages, without any observation of age-related changes. The Regenerative Index in DMD boys exhibited a decline between 7 and 11 years of age, with an inverse correlation between RI and age.</p><p><strong>Conclusions: </strong>The use of eMHC and IgG immunostaining to calculate RI appears to provide a way to assess regeneration across biopsies that differ in histopathologic severity. Using this approach, RI showed a negative correlation with age in DMD boys aged 7 to 11 years which requires further investigation.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13584490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148369667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting muscle fibrosis using non-specific collagenase injections destabilizes the basal lamina and induces matrix remodeling.","authors":"Ross P Wohlgemuth, Sathvik Sriram, Sarah E Brashear, Kyle E Henricson, Jason J Howard, Lucas R Smith","doi":"10.1186/s13395-026-00432-7","DOIUrl":"10.1186/s13395-026-00432-7","url":null,"abstract":"<p><strong>Background: </strong>Muscle passive and active function is dependent on the extracellular matrix (ECM). In diseases characterized by muscle fibrosis, namely Duchenne Muscular Dystrophy (DMD), the ECM contributes to deficits in muscle mechanical function and regeneration. Because fibrosis is often viewed as irreversible in DMD and other muscle diseases, there is great incentive to develop anti-fibrotic therapies to prevent or reverse fibrosis.</p><p><strong>Methods: </strong>In this study we tested the effectiveness of intramuscular injections of non-specific Clostridium histolyticum collagenase (CCH) on reducing ECM contents and rescuing muscle mechanical function in D2.mdx mice, models of DMD. We performed unilateral injections of collagenase into the tibialis anterior and gastrocnemius in WT and D2.mdx mice. We measured in vivo plantarflexion strength, ex vivo muscle mechanical function, immunohistochemistry, and total and cross-linked collagen content.</p><p><strong>Results: </strong>We found that crude CCH was effective at digesting the muscle ECM but did not provide a therapeutic benefit evidenced by induction of muscle weakness and bleeding within 24 h after CCH injections, and a thickened basal lamina after 7 days.</p><p><strong>Conclusions: </strong>We conclude that future studies testing collagenase as an anti-fibrotic should use a collagenase specific to fibrillar collagens and a paired physical therapy protocol to better preserve muscle function while reducing fibrosis.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13536639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148284355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elizabeth Chen is elected to the U.S. National Academy of Sciences.","authors":"Robert S Krauss","doi":"10.1186/s13395-026-00430-9","DOIUrl":"10.1186/s13395-026-00430-9","url":null,"abstract":"","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":"16 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13277079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148278593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combatting ventilator induced diaphragm dysfunction with human bone marrow mesenchymal stromal cell-derived extracellular vesicles.","authors":"Ya Wen, Xiang Zhang, Yvette Hedström, Nicola Cacciani, Jonas Bergquist, Y Ikeno, Oscar E Simonson, Sergey Rodin, Karl Henrik Grinnemo, Lars Larsson","doi":"10.1186/s13395-026-00433-6","DOIUrl":"10.1186/s13395-026-00433-6","url":null,"abstract":"<p><strong>Background: </strong>Prolonged mechanical ventilation is closely associated with ventilator-induced lung injury (VILI) and ventilator-induced diaphragm dysfunction (VIDD). These two conditions occur in parallel and contribute to delayed weaning, prolonged intensive care unit (ICU) stay, and poor clinical outcomes. This study evaluated whether human BM-MSC-derived extracellular vesicles (EVs) can simultaneously alleviate lung and diaphragm abnormalities in a unique rat experimental ICU (ExICU) model.</p><p><strong>Methods: </strong>Rats were subjected to 5 days of controlled mechanical ventilation with or without a single intravenous EV dose. Outcomes included lung histopathology, diaphragm single-fiber contractile function, transcriptomics and metabolomics of diaphragm muscle, proteomics and metabolomics of lung tissue, and serial proteomics of bronchoalveolar lavage fluid (BALF).</p><p><strong>Results: </strong>Five days of mechanical ventilation in the ExICU model were accompanied by severe lung morphological damage and approximately 50% reductions in diaphragm fiber size and specific force. EV treatment was associated with parallel improvements in lung pathology and diaphragm function. Multi-omics revealed coordinated molecular disturbances across lung, BALF, and diaphragm after mechanical ventilation, the majority of which were reversed by EVs.</p><p><strong>Conclusion: </strong>Our findings demonstrate an association between lung injury and diaphragm dysfunction during prolonged mechanical ventilation. BM-MSC-derived EVs exert parallel protective effects on both organs and represent a promising intervention to reduce complications of mechanical ventilation in critically ill patients.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13495324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancers integrate microenvironmental signals in muscle stem cells during regeneration in health, disease, and aging.","authors":"Sarah Hachmer, F Jeffrey Dilworth","doi":"10.1186/s13395-026-00434-5","DOIUrl":"10.1186/s13395-026-00434-5","url":null,"abstract":"<p><p>Effective skeletal muscle regeneration requires muscle stem cells (MuSCs) to continuously interpret and respond to signals from their surrounding microenvironment. These niche-derived cues, including inflammatory, extracellular matrix, paracrine, metabolic, and biomechanical signals, direct MuSC progression through quiescence, activation, proliferation, and differentiation by reshaping gene expression programs. Increasing evidence suggests that transcriptional enhancers serve as a key regulatory interface through which environmental information is translated into transcriptional output. Enhancer activity is governed by the coordinated action of lineage-defining transcription factors, histone modifiers, chromatin remodelers, transcriptional coactivators, and architectural proteins that together regulate chromatin accessibility, enhancer-promoter communication, and gene activation. Recent work has shown that enhancer landscapes and three-dimensional genome organization are highly dynamic during muscle regeneration and become altered in aging and disease. In this review, we examine how enhancer-associated mechanisms enable MuSCs to interpret niche-derived signals, highlighting the roles of transcription factor networks, chromatin remodeling complexes, and enhancer-promoter interactions in coordinating gene expression. We further discuss how disruption of enhancer regulation contributes to impaired regeneration in aging and muscular dystrophy, where altered chromatin states and genome organization lead to aberrant transcriptional responses. Understanding how these regulatory elements integrate complex environmental signals will be essential for defining the mechanisms underlying muscle regeneration and may provide new avenues for therapeutic intervention.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13488210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Declining muscle hyperplasia in juvenile trout is associated with a significant impairment of the supportive function of the myogenic progenitor niche.","authors":"Sabrina Jagot, Nathalie Sabin, Cécile Rallière, Adèle Branthonne, Morgane Chesnais, Cécile Duret, Jérôme Bugeon, Pierre-Yves Rescan, Karl Rouger, Jean-Charles Gabillard","doi":"10.1186/s13395-026-00431-8","DOIUrl":"10.1186/s13395-026-00431-8","url":null,"abstract":"<p><strong>Background: </strong>Unlike mammals and birds, where new muscle fiber formation (hyperplasia) ceases around birth, large and fast-growing fish such as trout undergo a spectacular post-hatching surge of hyperplasia, followed by a considerably delayed hyperplasia decline. This study investigated the role of muscle stem cells (MuSCs) and their niche in this process by assessing changes in their abundance, myogenic potential and niche functionality.</p><p><strong>Methods: </strong>Hyperplasia kinetics were investigated by measuring the total number of fibers and their cross-sectional area (CSA) in white muscle across juvenile stages (10 g to 2 kg). Quantification of MuSCs during growth was performed by pax7 in situ hybridization. To assess the supportive capacity of the MuSCs niche, muscle-derived cells (MDCs) extracted from the Tg(mlc2:gfp) trout line were transplanted into muscle of wild-type trout at different juvenile stages. Expression of GFP in transplanted muscle was measured as an indicator of myogenic progenitor differentiation.</p><p><strong>Results: </strong>Histological analysis revealed a significant decrease in hyperplasia and MuSCs density (defined here as pax7⁺ cells) between 10 and 500 g trout. Transplantation experiments using MDCs from Tg(mlc2:gfp) trout (10 g donors into 10 g to 2 kg recipients) showed alterations in niche functionality as the trout grew from 10 to 500 g. The transplantation of Tg(mlc2:gfp) MDCs from early to late juvenile donor trout (100 g to 2 kg) into 10 g WT recipients showed a decrease in the GFP signal as the donor weight increased. Detailed analyses of GFP⁺ fibers produced after transplantation showed an enrichment of small-CSA GFP⁺ fibers in 10 g but not 100 g trout recipient muscles, indicating a rapid impairment in niche ability to support hyperplasia. In addition, by comparing trout of the same age but different weights, we demonstrated that weight gain, rather than chronological aging, is a key factor driving this decline.</p><p><strong>Conclusions: </strong>Overall, these results indicate that the decline in muscle hyperplasia in trout is associated with an early impairment of the MuSC niche, along with a reduced MuSC density. Also, weight gain was found to play a more critical role than aging. These original findings provide new insights into the mechanisms underlying muscle growth as hyperplasia declines in vertebrates.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13474579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148206013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}