Satellite Cells Research Articles

Rapamycin improves satellite cells autophagy and muscle regeneration during hypercapnia.

Both CO2 retention, or hypercapnia, and skeletal muscle dysfunction predict higher mortality in critically ill patients. Mechanistically, muscle injury and reduced myogenesis contribute to critical illness myopathy, and while hypercapnia causes muscle wasting, no research has been conducted on hypercapnia-driven dysfunctional myogenesis in vivo. Autophagy flux regulates myogenesis by supporting muscle stem cell -satellite cell- activation, and previous data suggests that hypercapnia inhibits autophagy. We tested whether hypercapnia worsens satellite cell autophagy flux and myogenic potential, and if autophagy induction reverses these deficits. Satellite cell transplantation and lineage tracing experiments showed that hypercapnia undermines satellite cells activation, replication, and myogenic capacity. Bulk and single cell sequencing analyses indicated that hypercapnia disrupts autophagy, senescence, and other satellite cells programs. Autophagy activation was reduced in hypercapnic cultured myoblasts, and autophagy genetic knockdown phenocopied these changes in vitro. Rapamycin stimulation led to AMPK activation and downregulation of the mTOR pathway, which are both associated with accelerated autophagy flux and cell replication. Moreover, hypercapnic mice receiving rapamycin showed improved satellite cells autophagy flux, activation, replication rate, and post transplantation myogenic capacity. In conclusion, we have shown that hypercapnia interferes with satellite cell activation, autophagy flux and myogenesis, and systemic rapamycin administration improved these outcomes.

Effect of IGF1 on Myogenic Proliferation and Differentiation of Bovine Skeletal Muscle Satellite Cells Through PI3K/AKT Signaling Pathway

Effect of IGF1 on Myogenic Proliferation and Differentiation of Bovine Skeletal Muscle Satellite Cells Through PI3K/AKT Signaling Pathway

Impact of Alpha-Ketoglutarate on Skeletal Muscle Health and Exercise Performance: A Narrative Review.

AKG, a central metabolite in the Krebs cycle, plays a vital role in cellular energy production and nitrogen metabolism. This review explores AKG's potential therapeutic applications in skeletal muscle health and exercise performance, focusing on its mechanisms for promoting muscle regeneration and counteracting muscle atrophy. A literature search was conducted using the PubMed, Web of Science, and Scopus databases, yielding 945 articles published up to 31 October 2024. Of these, 112 peer-reviewed articles met the inclusion criteria and formed the basis of this review. AKG supports muscle recovery by stimulating muscle satellite cells (MuSCs) and macrophage polarization, aiding muscle repair and reducing fibrosis. Additionally, AKG shows promise in preventing muscle atrophy by enhancing protein synthesis, inhibiting degradation pathways, and modulating inflammatory responses, making it relevant in conditions like sarcopenia, cachexia, and injury recovery. For athletes and active individuals, AKG supplementation has enhanced endurance, reduced fatigue, and supported faster post-exercise recovery. Despite promising preliminary findings, research gaps remain in understanding AKG's long-term effects, optimal dosage, and specific pathways, particularly across diverse populations. Further research, including large-scale clinical trials, is essential to clarify AKG's role in muscle health and to optimize its application as a therapeutic agent for skeletal muscle diseases and an enhancer of physical performance. This review aims to provide a comprehensive overview of AKG's benefits and identify future directions for research in both clinical and sports settings.

An Insulin Upstream Open Reading Frame (INSU) Is Present in Skeletal Muscle Satellite Cells: Changes with Age.

Insulin resistance, stem cell dysfunction, and muscle fiber dystrophy are all age-related events in skeletal muscle (SKM). However, age-related changes in insulin isoforms and insulin receptors in myogenic progenitor satellite cells have not been studied. Since SKM is an extra-pancreatic tissue that does not express mature insulin, we investigated the levels of insulin receptors (INSRs) and a novel human insulin upstream open reading frame (INSU) at the mRNA, protein, and anatomical levels in Baltimore Longitudinal Study of Aging (BLSA) biopsied SKM samples of 27-89-year-old (yrs) participants. Using RT-qPCR and the MS-based selected reaction monitoring (SRM) assay, we found that the levels of INSR and INSU mRNAs and the proteins were positively correlated with the age of human SKM biopsies. We applied RNAscope fluorescence in situ hybridization (FISH) and immunofluorescence (IF) to SKM cryosections and found that INSR and INSU were co-localized with PAX7-labeled satellite cells, with enhanced expression in SKM sections from an 89 yrs old compared to a 27 yrs old. We hypothesized that the SKM aging process might induce compensatory upregulation of INSR and re-expression of INSU, which might be beneficial in early embryogenesis and have deleterious effects on proliferative and myogenic satellite cells with advanced age.

No detectable loss of myonuclei from human muscle fibers after six weeks of immobilization following an Achilles tendon rupture.

Muscle disuse has rapid and debilitating effects on muscle mass and overall health, making it an important issue from both scientific and clinical perspectives. However, the myocellular adaptations to muscle disuse are not yet fully understood, particularly those related to the myonuclear permanence hypothesis. Therefore, in this study, we assessed fiber size, number of myonuclei, satellite cells, and capillaries in human gastrocnemius muscle after a period of immobilization following an Achilles tendon rupture. Six physically active patients (5M/1F, 43 {plus minus} 15 years) were recruited to participate after sustaining an acute unilateral Achilles tendon rupture. Muscle biopsies were obtained from the lateral part of the gastrocnemius before and after six weeks of immobilization using a plaster cast and orthosis. Muscle fiber characteristics were analyzed in tissue cross-sections and isolated single fibers using immunofluorescence and high-resolution microscopy. Immobilization did not change muscle fiber type composition nor cross-sectional area of type I or type II fibers, but muscle fiber volume tended to decline by 13% (p=0.077). After immobilization, the volume per myonucleus was significantly reduced by 20% (p=0.008). Myonuclei were not lost in response to immobilization but tended to increase in single fibers and type II fibers. No significant changes were observed for satellite cells or capillaries. Myonuclei were not lost in the gastrocnemius muscle after a prolonged period of immobilization, which may provide support to the myonuclear permanence hypothesis in human muscle. Capillaries remained stable throughout the immobilization period, whereas the response was variable for satellite cells, particularly in type II fibers.

Identification of novel transcription factors regulated by H3K27 acetylation in myogenic differentiation of porcine skeletal muscle satellite cells.

H3K27 acetylation (H3K27ac) is crucial in muscle development as it regulates gene expression. Dysregulation of H3K27ac level has been linked to muscle-related diseases such as Duchenne muscular dystrophy, yet the mechanisms through which H3K27ac influences myogenic differentiation are not fully understood. Here, we utilized the SGC-CBP30 drug, a CBP/p300 bromodomain inhibitor, to reduce H3K27ac level and investigated its effect on myogenic differentiation of porcine skeletal muscle satellite cells. The results demonstrated an increased H3K27ac level during normal muscle satellite cell differentiation. We found that the addition of SGC-CBP30 resulted in a reduced level of H3K27ac based on ATAC-seq and CUT&Tag data. Our analysis revealed that a cluster characterized by reduced levels of H3K27ac and increased levels of H3K27me3 was enriched with motifs corresponding to Bach2, MafK, and Fosl2 transcription factors. Furthermore, knockdown of Bach2, MafK, and Fosl2 produced a similar suppression effect on myogenic differentiation. Taken together, our study contributes to a better understanding of how H3K27ac influences myogenic differentiation.

CircRNA profiling of skeletal muscle satellite cells in goats reveals circTGFβ2 promotes myoblast differentiation

BackgroundCircular RNAs (circRNAs) function as essential regulatory elements with pivotal roles in various biological processes. However, their expression profiles and functional regulation during the differentiation of goat myoblasts have not been thoroughly explored. This study conducts an analysis of circRNA expression profiles during the proliferation phase (cultured in growth medium, GM) and differentiation phase (cultured in differentiation medium, DM1/DM5) of skeletal muscle satellite cells (MuSCs) in goats.ResultsA total of 2,094 circRNAs were identified, among which 84 were differentially expressed as determined by pairwise comparisons across three distinct groups. Validation of the expression levels of six randomly selected circRNAs was performed using reverse transcription PCR (RT-PCR) and quantitative RT-PCR (qRT-PCR), with confirmation of their back-splicing junction sites. Enrichment analysis of the host genes associated with differentially expressed circRNAs (DEcircRNAs) indicated significant involvement in biological processes such as muscle contraction, muscle hypertrophy, and muscle tissue development. Additionally, these host genes were implicated in key signaling pathways, including Hippo, TGF-beta, and MAPK pathways. Subsequently, employing Cytoscape, we developed a circRNA-miRNA interaction network to elucidate the complex regulatory mechanisms underlying goat muscle development, encompassing 21 circRNAs and 47 miRNAs. Functional assays demonstrated that circTGFβ2 enhances myogenic differentiation in goats, potentially through a miRNA sponge mechanism.ConclusionIn conclusion, we identified the genome-wide expression profiles of circRNAs in goat MuSCs during both proliferation and differentiation phases, and established that circTGFβ2 plays a role in the regulation of myogenesis. This study offers a significant resource for the advanced exploration of the biological functions and mechanisms of circRNAs in the myogenesis of goats.

Therapeutic Potential of Melatonin: Multifaceted Applications in Muscle Health, Metabolic Disorders and Cardiovascular Disease

Melatonin, a hormone primarily synthesized by the pineal gland, is traditionally associated with the regulation of circadian rhythms. However, recent research has unveiled its broad spectrum of biological effects, positioning it as a valuable therapeutic agent in diverse health contexts. Known for its potent antioxidant and anti-inflammatory properties, melatonin plays a crucial role in maintaining homeostasis and protecting cellular integrity. This review explores melatonin’s therapeutic applications across multiple medical domains, including muscle health, metabolic disorders, chronic pain management, and cardiovascular health. In muscle health, melatonin facilitates muscle hypertrophy and regeneration by mitigating oxidative stress and enhancing the activity of satellite cells responsible for muscle repair. This action is particularly beneficial for individuals undergoing intense physical exertion, recovering from injuries, or combating age-related muscle. In metabolic disorders, such as type 2 diabetes, melatonin improves insulin sensitivity and reduces cellular oxidative damage, which supports beta-cell function and glucose regulation, potentially minimizing diabetes-related complications. Furthermore, in fibromyalgia - a condition marked by widespread pain and sleep disturbances - melatonin has demonstrated efficacy in alleviating pain and improving sleep quality, thus enhancing the overall quality of life for patients. In cardiovascular health, melatonin has shown promise in preventing and managing heart failure by reducing oxidative damage, modulating inflammatory pathways, and supporting endothelial function, which collectively contribute to improved cardiac health and reduced disease progression. This comprehensive review underscores melatonin’s emerging role as an integrative therapeutic agent in modern medicine.

Optimisation of cell fate determination for cultivated muscle differentiation

Production of cultivated meat requires defined medium formulations for the robust differentiation of myogenic cells into mature skeletal muscle fibres in vitro. Although these formulations can drive myogenic differentiation levels comparable to serum-starvation-based protocols, the resulting cultures are often heterogeneous, with a significant proportion of cells not participating in myofusion, limiting maturation of the muscle. To address this problem, we employed RNA sequencing to analyse heterogeneity in differentiating bovine satellite cells at single-nucleus resolution, identifying distinct cellular subpopulations including proliferative cells that fail to exit the cell cycle and quiescent ‘reserve cells’ that do not commit to myogenic differentiation. Our findings indicate that the MEK/ERK, NOTCH, and RXR pathways are active during the initial stages of myogenic cell fate determination, and by targeting these pathways, we can promote cell cycle exit while reducing reserve cell formation. This optimised medium formulation consistently yields fusion indices close to 100% in 2D culture. Furthermore, we demonstrate that these conditions enhance myotube formation and actomyosin accumulation in 3D bovine skeletal muscle constructs, providing proof of principle for the generation of highly differentiated cultivated muscle with excellent mimicry to traditional muscle.

Unraveling the bidirectional relationship between muscle inflammation and satellite cells activity: influencing factors and insights.

Inflammation stands as a vital and innate function of the immune system, essential for maintaining physiological homeostasis. Its role in skeletal muscle regeneration is pivotal, with the activation of satellite cells (SCs) driving the repair and generation of new myofibers. However, the relationship between inflammation and SCs is intricate, influenced by various factors. Muscle injury and repair prompt significant infiltration of immune cells, particularly macrophages, into the muscle tissue. The interplay of cytokines and chemokines from diverse cell types, including immune cells, fibroadipogenic progenitors, and SCs, further shapes the inflammation-SCs dynamic. While some studies suggest heightened inflammation associates with reduced SC activity and increased fibro- or adipogenesis, others indicate an inflammatory stimulus benefits SC function. Yet, the existing literature struggles to delineate clearly between the stimulatory and inhibitory effects of inflammation on SCs and muscle regeneration. This paper comprehensively reviews studies exploring the impact of pharmacological agents, dietary interventions, genetic factors, and exercise regimes on the interplay between inflammation and SC activity.

The unique functions of Runx1 in skeletal muscle maintenance and regeneration are facilitated by an ETS interaction domain.

The conserved Runt-related (RUNX) transcription factor family are master regulators of developmental and regenerative processes. Runx1 and Runx2 are expressed in satellite cells (SC) and in skeletal myotubes. Conditional deletion of Runx1 in adult SC negatively impacted self-renewal and impaired skeletal muscle maintenance even though Runx2 expression persisted. Runx1 deletion in C2C12 cells that retain Runx2 expression identified unique molecular functions of Runx1 that cannot be compensated by Runx2. The reduced myoblast fusion in vitro caused by Runx1 loss was due in part to ectopic expression of Mef2c, a target repressed by Runx1. Structure-function analysis demonstrated that the Ets-interacting MID/EID region of Runx1, absent from Runx2, is critical to Runx1 myoblast function and for Etv4 binding. Analysis of ChIP-seq datasets from Runx1 (T-cells, muscle) versus Runx2 (preosteoblasts) dependent tissues identified a composite Ets:Runx motif enriched in Runx1-dependent tissues. The Ets:Runx composite motif was enriched in peaks open exclusively in ATAC-seq datasets from WT cells compared to ATAC peaks unique to Runx1KO cells. Thus, engagement of a set of targets by the RUNX1/ETS complex define the non-redundant functions of Runx1.

SMN depletion impairs skeletal muscle formation and maturation in a mouse model of SMA.

Spinal muscular atrophy (SMA) is characterized by low levels of the ubiquitously expressed Survival Motor Neuron (SMN) protein, leading to progressive muscle weakness and atrophy. Skeletal muscle satellite cells play a crucial role in muscle fiber maintenance, repair, and remodelling. While the effects of SMN depletion in muscle are well documented, its precise role in satellite cell function remains largely unclear. Using the Smn2B/- mouse model, we investigated SMN-depleted satellite cell biology through single fiber culture studies. Myofibers from Smn2B/- mice were smaller in size, shorter in length, had reduced myonuclear domain size, and reduced sub-synaptic myonuclear clusters-all suggesting impaired muscle function and integrity. These changes were accompanied by a reduction in the number of myonuclei in myofibers from Smn2B/- mice across all disease stages examined. Although the number of satellite cells in myofibers was significantly reduced, those remaining retained their capacity for myogenic activation and proliferation. These findings support the idea that a dysregulated myogenic process could be occurring as early in muscle stem cells during muscle formation and maturation in SMA. Targeting those pathways could offer additional options for combinatorial therapies for SMA.

Autophagy in Muscle Regeneration: Mechanisms, Targets, and Therapeutic Perspective.

Autophagy maintains the stability of eukaryotic cells by degrading unwanted components and recycling nutrients and plays a pivotal role in muscle regeneration by regulating the quiescence, activation, and differentiation of satellite cells. Effective muscle regeneration is vital for maintaining muscle health and homeostasis. However, under certain disease conditions, such as aging, muscle regeneration can fail due to dysfunctional satellite cells. Dysregulated autophagy may limit satellite cell self-renewal, hinder differentiation, and increase susceptibility to apoptosis, thereby impeding muscle regeneration. This review explores the critical role of autophagy in muscle regeneration, emphasizing its interplay with apoptosis and recent advances in autophagy research related to diseases characterized by impaired muscle regeneration. Additionally, we discuss new approaches involving autophagy regulation to promote macrophage polarization, enhancing muscle regeneration. We suggest that utilizing cell therapy and biomaterials to modulate autophagy could be a promising strategy for supporting muscle regeneration. We hope that this review will provide new insights into the treatment of muscle diseases and promote muscle regeneration.

The Efficacy of Non-Steroidal Anti-Inflammatory Drugs in Athletes for Injury Management, Training Response, and Athletic Performance: A Systematic Review.

(1) Background: The purpose of this systematic review is to investigate the prevalent use of non-steroidal anti-inflammatory drugs (NSAIDs) in athletes and to comprehensively review the effectiveness and the results of these medications as it relates to injury management, training response, and overall sport performance. (2) Methods: An electronic literature search was performed in accordance with the recommendations and guidelines of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) protocol. A total of 7 randomized controlled studies met the review's specific inclusion criteria from the 2250 studies initially identified within the PubMed database. (3) Results: In total, 346 adult female and male athletes from a variety of sporting activities and fitness levels were observed, of which 175 athletes were treated with either oral, topical, or local muscular infusion of an NSAID. Depending on study design, the outcomes focused on results obtained through physical exam findings, questionnaires, various performance metrics, and direct tissue sampling from microdialysis or biopsies. Across the 7 total studies, 2 articles focused on injured athletes and their varying pain responses with NSAIDs; 2 studies assessed the limited impact of NSAIDs on performance; and 3 articles revealed the use of NSAIDs correlating to no increases in either collagen synthesis or satellite cell activity after exercise. (4) Conclusions: The systematic review affirmed that NSAIDs can be effective for managing acute pain. However, their value appears to diminish when treating chronic injuries or if NSAIDs are expected to improve performance or have other ergogenic effects in athletes, as the aggregate data did not support such benefits. (5) Practical applications: NSAIDs can be beneficial for athletes in the right situation, but the fact that there are risks and possible disadvantageous results with their use highlights the importance of promoting appropriate expectations and the judicious use of these medications with the athletic community.

Platelet-rich plasma ameliorates dexamethasone-induced myopathy by suppressing autophagy and enhancing myogenic potential through modulation of Myo-D, Pax-7, and myogenin expression

BackgroundMuscle tissue is essential for overall well-being that declines with age and different illnesses. Glucocorticoids, despite being efficient in treating inflammation, can induce muscle weakness (known as glucocorticoid-induced myopathy) by affecting protein breakdown and synthesis. Glucocorticoids have a negative impact on satellite cells, which play a role in muscle regeneration. Platelet rich plasma (PRP), containing concentrated growth factors, has a potential role in enhancing tissue repair and could be used to ameliorates combat muscle wasting caused by glucocorticoids. AimThe purpose of this study was to identify how PRP can affect dexamethasone-induced myopathy in a rat model. MethodsTwenty-four male rats were divided into four equal groups: control, PRP, steroid (dexamethasone) treated for induction of myopathy, and steroid then treated with PRP for three weeks. Skeletal muscle contractile properties, protein content of the muscle, oxidative stress markers, histological structure, myogenin gene expression and immunohistochemical expression of Myo-D, Pax-7 and LC3 were assessed. Resultsdexamethasone caused significant muscle weakness, decreased protein content, increased oxidative stress, decreased expression of myogenic genes and upregulated LC3 expression. PRP administration significantly improved muscle function, increased protein content, reduced oxidative stress, and upregulated myogenic genes. Histological results confirmed these findings. Additionally, PRP decreased autophagy marker LC3 expression and increased muscle stem cell markers MyoD and Pax7. ConclusionThese results suggested that PRP could effectively prevent and reverse dexamethasone-induced muscle atrophy by promoting muscle protein synthesis, reducing oxidative stress, decreasing autophagy, and enhancing muscle stem cell activity. This study supports the potential role of PRP as a therapeutic strategy for muscle wasting disorders.

Effect of NR1D1 on the proliferation and differentiation of yak skeletal muscle satellite cells.

The severe conditions at high altitudes, where yaks inhabit, contribute to delayed muscular growth and compromised tenderness of their muscle tissue. Myosatellite cells are responsible for the growth and regeneration of skeletal muscle after birth and have the potential to proliferate and differentiate, its development is closely related to meat quality, and the nuclear receptor gene NR1D1 is involved in muscle formation and skeletal muscle regulation. Therefore, in order to understand the effect of NR1D1 on muscle satellite cells, we identified the mRNA expression levels of marker genes specifically expressed in muscle satellite cells at different stages to determine the type of cells isolated. Eventually, we successfully constructed a primary cell line of yak muscle satellite cells. Then we constructed NR1D1 overexpression vector and interference RNA, and introduced them into isolated yak skeletal muscle satellite cells. We performed qPCR, CCK8, and fluorescence-specific to detect the expression of genes or abundance of proteins as markers of cell proliferation and differentiation. Compared with those in the control group, the expression levels of proliferation marker genes KI-67, CYCLIND1, and CYCLINA were significantly inhibited after NR1D1 overexpression, which was also supported by the CCK-8 test, whereas differentiation marker genes MYOD, MYOG, and MYF5 were significantly inhibited. Fluorescence-specific staining showed that KI-67 protein abundance and the number of microfilaments both decreased, while the opposite trend was observed after NR1D1 interference. In conclusion, we confirmed that NR1D1 inhibited the proliferation and differentiation of yak skeletal muscle satellite cells, which provides a theoretical basis for further research on the effect of NR1D1 on improving meat quality traits and meat production performance of yaks.

TLR7/8 Activation in Immune Cells and Muscle by RNA-Containing Immune Complexes: Role in Inflammation and the Pathogenesis of Myositis.

Activation of endosomal toll-like receptors (TLRs) is one possible driver of inflammation in idiopathic inflammatory myopathies (IIM). We investigated the potential contribution of TLR7 and TLR8 to IIM pathogenesis. Activation of TLR7/8 in healthy donor peripheral blood mononuclear cells (PBMCs) by immune complexes from patients with IIMs and lupus was tested. Autoantibody profiling of patient IgG samples was performed using a 1581 antigen array. TLR7 and/or TLR8 activation by RNA molecules associated with autoantibodies was assessed. Gene expression in human myoblasts and satellite cells following treatment with supernatants from TLR7/8-activated PBMCs was evaluated by NanoString. C57BL/6 mice were dosed intramuscularly with the TLR7/8 agonist R848 and single-cell RNA-sequencing was performed on the muscle to ascertain the cell types responding to TLR7/8 activation and the downstream effects. Overall, 69 patients with IIMs were included with representation of dermatomyositis, polymyositis, and inclusion body myositis subsets. Immune complexes from patients with IIMs, as well as autoantibody-associated RNAs histidyl-transfer RNA, Y1, Y4, and U1, activated PBMCs to produce interferon-α and IL-6 via TLR7/8. Several canonical (Ro60, Ro52, and HIST1H4A) and novel (IL-36RN) autoreactivities correlated highly with TLR7/8 activation. Supernatants from TLR7/8-activated PBMCs had a negative impact on human myoblasts and satellite cells. Endothelial cells were activated by R848 in mouse muscle in vivo in addition to immune cells such as monocytes and macrophages. Our results suggest that patients with IIMs have autoantibodies in their blood causing TLR7/8 activation, which leads to inflammation in muscles with potential deleterious effects.

The Effect of Multi-Ingredient Protein versus Collagen Supplementation on Satellite Cell Properties in Males and Females.

Skeletal muscle satellite cells (SC) contribute to the adaptive process of resistance exercise training (RET) and may be influenced by nutritional supplementation. However, little research exists on the impact of multi-ingredient supplementation on the SC response to RET. We tested the effect of a multi-ingredient supplement (MIS) including whey protein, creatine, leucine, calcium citrate, and vitamin D on SC content and activity as well as myonuclear accretion, SC and myonuclear domain compared with a collagen control (COL) throughout a 10-wk RET program. Twenty-six participants underwent a 10-wk linear RET program while consuming either the MIS or COL supplement twice daily. Muscle biopsies were taken from the vastus lateralis at baseline and 48 h after a bout of damaging exercise, before and after RET. Muscle tissue was analyzed for SC and myonuclear content, domain, acute SC activation, and fiber cross-sectional area (fCSA). MIS resulted in a greater increase in type II fCSA following 10 wk of RET (effect size (ES) = 0.89) but not myonuclear accretion or SC content. Change in myonuclei per fiber was positively correlated with type I and II and total fiber hypertrophy in the COL group only, indicating a robust independent effect of MIS on fCSA. Myonuclear domain increased similarly in both groups, whereas SC domain remained unchanged following RET. SC activation was similar between groups for all fiber types in the untrained state but showed a trend toward greater increases with MIS after RET (ES = 0.70). SC responses to acute damaging exercise and long-term RET are predominantly similar in MIS and COL groups. However, MIS can induce greater increases in type II fCSA with RET and potentially SC activation following damage in the trained state.

Role of the transcription factor PAX3 during myogenesis: from the embryo to the adult stage

PAX3 plays a crucial role in embryonic myogenesis, controlling the specification, migration, proliferation, and differentiation of muscle progenitor cells to ensure normal skeletal muscle development in the embryo. However, PAX3 potential role in a context of muscle homeostasis and regeneration remains poorly investigated. The adult muscle stem cells, known as satellite cells (SCs) exhibit heterogeneity in Pax3 expression in various muscles throughout the body and display a bimodal response to environmental stress exposure. To explore the role of PAX3 in the context of tissue damage, we performed regeneration studies, which unveiled a functional heterogeneity of the SCs populations depending on Pax3 expression. Together, this project aims to decipher cell-type specific dysregulations linked to tissue damage and identify PAX3 downstream gene regulatory networks that can lead to specific SC behavior, thus potentially providing novel strategies for muscle disease preventive therapies.

Menstrual cycle phase differences in myofiber damage and macrophage infiltration following electrical stimulation-induced muscle injury.

The purpose of this study was to examine the effects of menstrual cycle phase on myofiber injury, regenerative events and inflammation after electrical-stimulation (ES) induced myofiber damage. 28 premenopausal women (21.3 ± 2 yrs) were randomized into an early follicular (EF; N=14) or late follicular (LF; N = 14) group. After menstrual cycle tracking and phase confirmation, subjects underwent 200 electrically stimulated eccentric muscle contractions one week after providing a muscle biopsy. 7 days post-ES, subjects provided a final biopsy. Primary outcomes included: serum estradiol, indirect markers of muscle damage, direct indicators of myofiber necrosis and regeneration, satellite cell number, and macrophage infiltration. Women in the LF group had higher serum estradiol (122.1 ± 23.4 vs. 81.7 ± 30.8 pg/ml; P<0.001)compared to the EF group on the day of ES. Whereas the EF group recovered baseline maximal isometric strength by 4 days post-ES, the LF group did not. Only women in the LF group showed significant and consistent evidence of myofiber necrosis and regeneration pre- to post-ES. Despite showing more evidence of myofiber damage, women in the LF group also experienced reduced total and CD206+ macrophage infiltration relative to the EF group. Satellite cell quantity increased significantly post-ES in both groups, with no differences between groups. Collectively, the data suggest that the high estrogen LF phase may be associated with increased susceptibility to myofiber injury while also limiting the subsequent intramuscular inflammatory response.