Multi-transcriptome analysis following an acute skeletal muscle growth stimulus yields tools for discerning global and MYC regulatory networks

Journal of Biological Chemistry, Journal Year: 2022, Volume and Issue: 298(11), P. 102515 - 102515

Published: Sept. 21, 2022

Myc is a powerful transcription factor implicated in epigenetic reprogramming, cellular plasticity, and rapid growth as well tumorigenesis. Cancer skeletal muscle extremely rare despite marked sustained induction during loading-induced hypertrophy. Here, we investigated global, actively transcribed, stable, myonucleus-specific transcriptomes following an acute hypertrophic stimulus mouse plantaris. With these datasets, define global Myc-specific dynamics at the onset of mechanical overload-induced fiber growth. Data collation across analyses reveals under-appreciated role for extracellular matrix remodeling adaptation, along with contribution mRNA stability to epigenetic-related transcript levels muscle. We also identify Runx1 Ankrd1 (Marp1) abundant myonucleus-enriched genes. observed that strong cell cycle regulators including occurs overload myonuclei. Additionally, vivo Myc-controlled gene expression plantaris was defined using genetic fiber-specific doxycycline-inducible Myc-overexpression model. determined numerous aspects early-phase Specifically, brief protein represses Reverbα, Reverbβ, Myh2 while increasing Rpl3, recapitulating myonuclei overload. Experimental, comparative, silico place center stable loading-responsive, fiber-localized regulatory hub. Collectively, our experiments are roadmap understanding Myc-mediated transcriptional networks regulate postmitotic cells. provide open webtools exploring five RNA-seq datasets resource field.

Language: Английский

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A molecular signature defining exercise adaptation with ageing and in vivo partial reprogramming in skeletal muscle

The Journal of Physiology, Journal Year: 2022, Volume and Issue: 601(4), P. 763 - 782

Published: Dec. 19, 2022

Abstract Exercise promotes functional improvements in aged tissues, but the extent to which it simulates partial molecular reprogramming is unknown. Using transcriptome profiling from (1) a skeletal muscle‐specific vivo Oct3/4 , Klf4 Sox2 and Myc (OKSM) reprogramming‐factor expression murine model; (2) an inducible induction (3) translatable high‐volume hypertrophic exercise training approach mice; (4) human muscle biopsies, we collectively defined exercise‐induced genes that are common reprogramming. Late‐life lowered DNA methylation age according several contemporary clocks. A comparison of soleus after late‐life OKSM revealed overlapping signature included higher JunB Sun1 . Also, within this signature, downregulation specific mitochondrial muscle‐enriched was conserved long‐term exercise‐trained humans; among these Abra/Stars factor most induced by elevated following mice. pulse MYC rewired global methylome, partially recapitulated induction. also emerged MYC‐controlled adaptation transcriptomes, including lower Melusin reactive oxygen species‐associated Romo1 With mice, as well habitual humans, complex I accessory subunit Ndufb11 lower; low linked longevity rodents. Collectively, shares similarities with genetic image Key points Advances last decade related cellular epigenetic (e.g. methylome remodelling) toward pluripotent state via Yamanaka transcription factors provide window into potential mechanisms for combatting deleterious effects ageing. gene analysis, compared OKSM‐mediated fibres mice muscle. muscle, so factor‐mediated mRNA landscapes humans. single sufficient remodel methylome. We identify reprogramming‐associated innately altered propose contributes some responses.

Language: Английский

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Exome-Wide Association Study of Competitive Performance in Elite Athletes

Genes, Journal Year: 2023, Volume and Issue: 14(3), P. 660 - 660

Published: March 6, 2023

The aim of the study was to identify genetic variants associated with personal best scores in Turkish track and field athletes compare allelic frequencies between sprint/power endurance controls using a whole-exome sequencing (WES) approach, followed by replication studies independent cohorts. discovery phase involved 60 elite (31 29 endurance) 20 ethnically matched controls. 1132 individuals (115 Russian sprinters, 373 (of which 75 were VO2max measurements), 209 controls, 148 287 Finnish muscle fiber composition cross-sectional area (CSA) data). None single nucleotide polymorphisms (SNPs) reached an exome-wide significance level (p < 2.3 × 10−7) genotype–phenotype case–control athletes. However, 53 nominally 0.05) SNPs, four functional replicated. SIRT1 rs41299232 G allele significantly over-represented = 0.047) 0.018) compared increased 0.037) greater proportion slow-twitch fibers 0.035). NUP210 rs2280084 A 0.044) 0.012) TRPM2 rs1785440 0.034) 0.008). AGRN rs4074992 C CSA fast-twitch 0.024). In conclusion, we present first WES showing that this approach can be used novel markers exercise- sport-related phenotypes.

Language: Английский

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Methylome–proteome integration after late‐life voluntary exercise training reveals regulation and target information for improved skeletal muscle health

The Journal of Physiology, Journal Year: 2024, Volume and Issue: 603(1), P. 211 - 237

Published: July 26, 2024

Exercise is a potent stimulus for combatting skeletal muscle ageing. To study the effects of exercise on in preclinical setting, we developed combined endurance-resistance training mice called progressive weighted wheel running (PoWeR). PoWeR improves molecular, biochemical, cellular and functional characteristics promotes aspects partial epigenetic reprogramming when performed late life (22-24 months age). In this investigation, leveraged pan-mammalian DNA methylome arrays tandem mass-spectrometry proteomics to provide detailed information late-life adaptations female relative age-matched sedentary controls (n = 7-10 per group). Differential CpG methylation at conserved promoter sites was related transcriptional regulation genes as well Nr4a3, Hes1 Hox after PoWeR. Using holistic method -omics integration binding expression target analysis (BETA), changes were associated with upregulated proteins global mitochondrial translation (P 0.03). Specifically, BETA implicated control ribosomal, mitoribosomal, complex I protein abundance training. may also influence LACTB, MIB1 UBR4 induction - all are mechanistically linked health. Computational cistrome predicted several transcription factors including MYC regulators trained methylome-proteome landscape, corroborating prior transcriptome data. Correlating proteome mass fatigue resistance revealed positive relationships VPS13A NPL levels, respectively. Our findings expose differential proteomic translational that could function aged mice. KEY POINTS: Late-life from 22-24 age shown improve vivo promote mitigation. Integration 36k using (which contain ageing clock sites) exploratory extends our work reveals coordinated widespread initiation, ribosomal (mitoribosomal) voluntary sizeable cohort group analysis). Multi-omics serine β-lactamase-like (LACTB tumour muscle), mind bomb 1 (MIB1 satellite cell type 2 fibre maintenance) ubiquitin ligase E3 component N-recognin 4 (UBR4 quality control) identified regulator proteome, agreement analyses. Vacuolar sorting 13 homolog A (VPS13A) positively correlated mass, glycoprotein/glycolipid sialylation enzyme N-acetylneuraminate pyruvate lyase (NPL) resistance.

Language: Английский

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The 24-hour molecular landscape after exercise in humans reveals MYC is sufficient for muscle growth

EMBO Reports, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 31, 2024

Language: Английский

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Resistance and endurance exercise training improves muscle mass and the inflammatory/fibrotic transcriptome in a rhabdomyosarcoma model

Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2023, Volume and Issue: 14(2), P. 781 - 793

Published: Feb. 16, 2023

Rhabdomyosarcoma (RMS) is an aggressive soft tissue sarcoma that most often develops in children. Chemoradiation therapy a standard treatment modality; however, the detrimental long-term skeletal muscle consequences of this juvenile cancer survivors include atrophy and fibrosis resulting decreased physical performance. Using novel model murine resistance endurance exercise training, we investigate its role preventing effects RMS plus therapy.Four-week-old male (n = 10) female C57Bl/6J mice were injected with M3-9-M cell into left gastrocnemius right limb serving as internal control (CON). Mice received systemic vincristine injection then five doses 4.8 Gy gamma radiation localized to hindlimb (RMS + Tx). randomly divided either sedentary (SED) or training (RET) groups. Changes performance, body composition, myocellular adaptations inflammatory/fibrotic transcriptome assessed.RET improved performance (P < 0.0001) composition 0.0004) compared SED. Tx resulted significantly lower weight 0.015) smaller myofibre cross-sectional area (CSA) 0.014). Conversely, RET higher 0.030) larger Type IIA 0.014) IIB fibre CSA. more 0.028), which was not prevented by RET. fewer mononuclear cells 0.05) satellite (stem) (MuSCs) immune than CON. fibro-adipogenic progenitors 0.05), trend for MuSCs 0.076) SED endothelial specifically limb. Transcriptomic changes revealed expression inflammatory fibrotic genes Tx, In model, also altered involved extracellular matrix turnover.Our study suggests preserves mass survivorship while partially restoring cellular dynamics transcriptome.

Language: Английский

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Dynamic of irisin secretion change after moderate-intensity chronic physical exercise on obese female

Journal of Basic and Clinical Physiology and Pharmacology, Journal Year: 2023, Volume and Issue: 34(4), P. 539 - 547

Published: May 20, 2023

Exercise is one of the beneficial mediators for regulation and prevention obesity through role irisin, so it potentially enhances metabolism health. This study aims to investigate dynamic irisin secrecy change after chronic exercise in obese females.Thirty-one female adolescents aged 20-22 years enrolled were given interventions aerobic, resistance, a combination aerobic resistance training. The exercises performed at moderate-intensity, 35-40 min per session, three times week four weeks. measurement level, IGF-1 bio-anthropometry was carried out before weeks exercise. using seca mBCA 514, while insulin-like growth factor 1 (IGF-1) completed an enzyme-linked immunosorbent assay (ELISA). obtained data analyzed one-way ANOVA test with 5 % significance.Our results indicated higher increases group training than other two groups different Further, we also observed dynamics level increase (p<0.05). Besides, correlated bio-anthropometric parameters (p<0.05).The considered as alternative enhancing increase. Thus, can be used prevent regulate obesity.

Language: Английский

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The 24-Hour Time Course of Integrated Molecular Responses to Resistance Exercise in Human Skeletal Muscle ImplicatesMYCas a Hypertrophic Regulator That is Sufficient for Growth

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 27, 2024

Abstract Molecular control of recovery after exercise in muscle is temporally dynamic. A time course biopsies around resistance (RE) combined with -omics necessary to better comprehend the molecular contributions skeletal adaptation humans. Vastus lateralis before and 30 minutes, 3-, 8-, 24-hours acute RE were collected. time-point matched biopsy-only group was also included. RNA-sequencing defined transcriptome while DNA methylomics computational approaches complemented these data. The post-RE revealed: 1) methylome responses at minutes corresponded upregulated genes 3 hours, 2) a burst translation- transcription-initiation factor-coding transcripts occurred between 8 3) global gene expression peaked 4) ribosome-related dominated mRNA landscape 24 5) methylation-regulated MYC highly influential transcription factor throughout 24-hour played primary role levels hours. influence human strengthened by information from overexpression mouse muscle. To test whether sufficient for hypertrophy, we generated fiber-specific doxycycline inducible model pulsatile induction. Periodic 48-hour pulses over 4 weeks resulted higher mass fiber size soleus adult female mice. Collectively, present resolved resource understanding adaptations reveal as regulator RE-induced hypertrophy.

Language: Английский

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Effects of defined voluntary running distances coupled with high‐fat diet consumption on the skeletal muscle transcriptome of male mice

Physiological Reports, Journal Year: 2025, Volume and Issue: 13(2)

Published: Jan. 1, 2025

Abstract Exercise counters many adverse health effects of consuming a high‐fat diet (HFD). However, complex molecular changes that occur in skeletal muscle response to exercising while HFD are not yet known. We investigated the interplay between diverse exercise regimes and consumption on adaptation transcriptome. C57BL/6 male mice were randomized into five groups—one sedentary control group four groups. The groups consisted an unrestricted running (8.3 km/day) three restricted 75%, 50%, or 25% (6.3, 4.2, 2.1 km/day, respectively). Total RNA was extracted from frozen gastrocnemius for transcriptome analyses. DEG counts 1347, 1823, 1103, 1107 there 107, 169, 67, 89 unique genes present HFD‐25%, HFD‐50%, HFD‐75%, HFD‐U, respectively. Comparing groups, we found at 50% resulted most differentially expressed transcripts with MAPK PPAR signaling pathways enriched down‐ up‐regulated genes, These results demonstrate distance impacts suggest middle‐distance may provide greatest protection against diet‐induced stress coupled exercise.

Language: Английский

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A primer on global molecular responses to exercise in skeletal muscle: Omics in focus

Journal of sport and health science/Journal of Sport and Health Science, Journal Year: 2025, Volume and Issue: unknown, P. 101029 - 101029

Published: Feb. 1, 2025

Advances in skeletal muscle omics has expanded our understanding of exercise-induced adaptations at the molecular level. Over past 2 decades, transcriptome studies have detailed acute and chronic responses to resistance, endurance, concurrent exercise, focusing on variables such as training status, nutrition, age, sex, metabolic health profile. Multi-omics approaches, integration transcriptomic epigenetic data, along with emerging ribosomal RNA sequencing advancements, further provided insights into how adapts exercise across lifespan. Downstream transcriptome, proteomic phosphoproteomic identified novel regulators adaptations, while single-cell/nucleus spatial technologies promise evolve cellular specialization communication around cells. This narrative review highlights (a) historical foundations muscle, (b) current research 3 layers cascade (DNA, RNA, protein), (c) applications single-cell study adaptation exercise. Further elaboration muscle's global footprint using multi-omics methods will help researchers practitioners develop more effective targeted approaches improve well athletic performance.

Language: Английский

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