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This study investigates the transcriptome-level alterations that influence production traits and early fattening stage myogenesis in Hanwoo cattle, specifically focusing on the highly prized Longissimus dorsi (LD) and Psoas major (PM) skeletal muscles, which hold significant commercial value. We conducted RNA sequencing analysis on LD and PM muscles from 14 Hanwoo steers (n = 7, each group) at the age of 10 months, all fed the same diet. Our results unveiled a total of 374 and 206 up-regulated differentially expressed genes (DEGs) in LD and PM muscles, respectively, with statistical significance (p < 0.05) and a log2fold change ≥ 1. Genes governing muscle development processes, such as PAX3, MYL3, COL11A1, and MYL6B, were found to be expressed at higher levels in both tissues. Conversely, genes regulating lipid metabolism, including FABP3, FABP4, LEP, ADIPOQ, and PLIN1, exhibited higher expression in the PM muscle. Functional enrichment analysis revealed a tissue-specific response, as PM muscle showed increased lipid metabolism allied pathways, including the PPAR signaling pathway and regulation of lipolysis in adipocytes, while LD was characterized by growth and proliferative processes. Our findings validate the presence of a muscle-dependent transcription and co-expression pattern that elucidates the transcriptional landscape of bovine skeletal muscle.
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Water temperature is a crucial environmental factor that significantly affects the physiological and biochemical processes of fish. Due to the occurrence of cold events in aquaculture, it is imperative to investigate how fish respond to cold stress. This study aims to uncover the mechanisms responds to acute cold stress by conducting a comprehensive analysis of the histomorphology, glycolipid metabolic and antioxidant enzymes, fatty acid composition and transcriptome at three temperatures (16 °C, 10 °C and 4 °C) in Phoxinus lagowskii. Our results showed that cold stress not damaged muscle microstructure but caused autophagy (at 10 °C). In addition, serum glucose (Glu) and triglycerides (TG) increased during cold stress. The activities of reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), fructose phosphokinase (PFK), hexokinase (HK), pyruvate kinase (PK), and malondialdehyde (MDA) content in muscle were measured and analyzed. During cold stress, superoxide dismutase and catalase activities increased, reactive oxygen species content decreased. No significant difference in Glutathione peroxidase (GPx) activity, malondialdehyde and total cholesterol (T-CHO) contents among groups. Phosphokinase and pyruvate kinase activities decreased, and HK activity increased during cold stress. Our study resulted in the identification of a total of 25,400 genes, with 2524 genes showing differential expression across different temperature treatments. Furthermore, KEGG pathway indicated that some pathways upregulated during light cold stress (at 10 °C, including autophagy, and AMP-activated protein kinase (AMPK) signaling pathway. Additionally, circadian rhythm is among the most enriched pathways in genes up-regulated during severe cold stress (at 4 °C). Our findings offer valuable insights into how cold-water fish respond to cold stress.
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Antioxidantes , Respuesta al Choque por Frío , Cyprinidae , Ácidos Grasos , Glucolípidos , Animales , Cyprinidae/genética , Cyprinidae/fisiología , Cyprinidae/metabolismo , Ácidos Grasos/metabolismo , Antioxidantes/metabolismo , Glucolípidos/metabolismo , Transcriptoma , Perfilación de la Expresión GénicaRESUMEN
Growth rate is a commercial trait in aquaculture that is influenced by multiple factors, among which genetic composition plays a fundamental role in the growth rate of species. The phoenix barb (Spinibarbus denticulatus denticulatus) is a widely distributed freshwater fish species in South China. Although S. d. denticulatus is reared in South China, the molecular mechanisms underlying the growth rate of the species remain unclear. Here, the authors performed transcriptome analysis of muscle tissues from fast-growing (FG) and slow-growing (SG) S. d. denticulatus at 90, 150, and 300 days after hatch (DAH) to elucidate its growth mechanism. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that differentially expressed genes (DEGs) between the two groups were enriched in pathways related to muscle growth, glycolysis, and energy and lipid metabolism. Nonetheless, a higher number of DEGs were identified in the FG vs. SG groups at 90 and 300 DAH compared with 150 DAH. DEGs identified at 90 DAH were mainly enriched in the GH/IGF axis, PI3K-Akt signalling pathway, AMPK signalling pathway and lipid metabolism highly expressed in FG individuals. DEGs identified at 300 DAH were mainly enriched in PI3K-Akt signalling pathway, glycolysis/gluconeogenesis, gene translation and lipid metabolism. In addition, some genes were expressed during the early growth stage in FG individuals but expressed during the late stage in SG individuals, indicating considerable variations in the expression profiles of growth-related genes at different developmental stages. Overall, these findings contribute to the understanding of the growth mechanism of S. d. denticulatus, which would be useful for the propagation of fast-growing breeds.
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Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Animales , Proteínas Proto-Oncogénicas c-akt/genética , Perfilación de la Expresión Génica , Músculos , Genoma , TranscriptomaRESUMEN
On-growing juveniles of gilthead sea bream were acclimated for 45 days to mild-hypoxia (M-HYP, 40-60% O2 saturation), whereas normoxic fish (85-90% O2 saturation) constituted two different groups, depending on if they were fed to visual satiety (control fish) or pair-fed to M-HYP fish. Following the hypoxia conditioning period, all fish were maintained in normoxia and continued to be fed until visual satiation for 3 weeks. The time course of hypoxia-induced changes was assessed by changes in blood metabolic landmarks and muscle transcriptomics before and after exhaustive exercise in a swim tunnel respirometer. In M-HYP fish, our results highlighted a higher contribution of aerobic metabolism to whole energy supply, shifting towards a higher anaerobic fitness following normoxia restoration. Despite these changes in substrate preference, M-HYP fish shared a persistent improvement in swimming performance with a higher critical speed at exercise exhaustion. The machinery of muscle contraction and protein synthesis and breakdown was also largely altered by mild-hypoxia conditioning, contributing this metabolic re-adjustment to the positive regulation of locomotion and to the catch-up growth response during the normoxia recovery period. Altogether, these results reinforce the presence of large phenotypic plasticity in gilthead sea bream, and highlights mild-hypoxia as a promising prophylactic measure to prepare these fish for predictable stressful events.
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OBJECTIVES: The Brown trout is a salmonid species with a high commercial value in Europe. Life history and spawning behaviour include resident (Salmo trutta m. fario) and migratory (Salmo trutta m. trutta) ecotypes. The main objective is to apply RNA-seq technology in order to obtain a reference transcriptome of two key tissues, brain and muscle, of the riverine trout Salmo trutta m. fario. Having a reference transcriptome of the resident form will complement genomic resources of salmonid species. DATA DESCRIPTION: We generate two cDNA libraries from pooled RNA samples, isolated from muscle and brain tissues of adult individuals of Salmo trutta m. fario, which were sequenced by Illumina technology. Raw reads were subjected to de-novo transcriptome assembly using Trinity, and coding regions were predicted by TransDecoder. A final set of 35,049 non-redundant ORF unigenes were annotated. Tissue differential expression analysis was evaluated by Cuffdiff. A False Discovery Rate (FDR) ≤ 0.01 was considered for significant differential expression, allowing to identify key differentially expressed unigenes. Finally, we have identified SNP variants that will be useful tools for population genomic studies.
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Transcriptoma , Trucha , Animales , Encéfalo , Músculos , Transcriptoma/genética , Trucha/genéticaRESUMEN
BACKGROUND: Coexpression network analysis is a powerful tool to reveal transcriptional regulatory mechanisms, identify transcription factors, and discover gene functions. It can also be used to investigate changes in coexpression patterns in response to environmental insults or changes in experimental conditions. Maternal nutrition is considered a major intrauterine regulator of fetal developmental programming. The objective of this study was to investigate structural changes in gene coexpression networks in the muscle of bull beef calves gestated under diets with or without methionine supplementation. Both muscle transcriptome and methylome were evaluated using next generation sequencing. RESULTS: Maternal methionine supplementation significantly perturbed coexpression patterns in the offspring's muscle. Indeed, we found that neither the connection strength nor the connectivity pattern of six modules (subnetworks) detected in the control diet were preserved in the methionine-rich diet. Functional characterization revealed that some of the unpreserved modules are implicated in myogenesis, adipogenesis, fibrogenesis, canonical Wnt/ß-catenin pathway, ribosome structure, rRNA binding and processing, mitochondrial activities, ATP synthesis and NAD(P) H oxidoreductases, among other functions. The bisulfite sequencing analysis showed that nearly 2% of all evaluated cytosines were differentially methylated between maternal diets. Interestingly, there were significant differences in the levels of gene body DNA methylation between preserved and unpreserved modules. CONCLUSIONS: Overall, our findings provide evidence that maternal nutrition can significantly alter gene coexpression patterns in the offspring, and some of these perturbations are mediated by changes in DNA methylation.
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Bovinos/genética , Músculo Esquelético/metabolismo , Fenómenos Fisiologicos de la Nutrición Prenatal , Transcriptoma , Animales , Bovinos/metabolismo , Dieta , Femenino , Redes Reguladoras de Genes , Masculino , Metionina/metabolismo , Desarrollo de Músculos , Músculo Esquelético/crecimiento & desarrollo , EmbarazoRESUMEN
Improvement of feed efficiency (FE) is key for Sustainability and cost reduction in pig production. Our aim was to characterize the muscle transcriptomic profiles in Danbred Duroc (Duroc; n = 13) and Danbred Landrace (Landrace; n = 28), in relation to FE for identifying potential biomarkers. RNA-seq data on the 41 pigs was analyzed employing differential gene expression methods, gene-gene interaction and network analysis, including pathway and functional analysis. We also compared the results with genome regulation in human exercise data, hypothesizing that increased FE mimics processes triggered in exercised muscle. In the differential expression analysis, 13 genes were differentially expressed, including: MRPS11, MTRF1, TRIM63, MGAT4A, KLH30. Based on a novel gene selection method, the divergent count, we performed pathway enrichment analysis. We found five significantly enriched pathways related to feed conversion ratio (FCR). These pathways were mainly related to mitochondria, and summarized in the mitochondrial translation elongation (MTR) pathway. In the gene interaction analysis, the most interesting genes included the mitochondrial genes: PPIF, MRPL35, NDUFS4 and the fat metabolism and obesity genes: AACS, SMPDL3B, CTNNBL1, NDUFS4, and LIMD2. In the network analysis, we identified two modules significantly correlated with FCR. Pathway enrichment of module genes identified MTR, electron transport chain and DNA repair as enriched pathways. The network analysis revealed the mitochondrial gene group NDUF as key network hub genes, showing their potential as biomarkers. Results show that genes related to human exercise were enriched in identified FCR related genes. We conclude that mitochondrial activity is a key driver for FCR in muscle tissue, and mitochondrial genes could be potential biomarkers for FCR in pigs.
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BACKGROUND: Supplementing farm animals diet with functional ingredients may improve the nutritional quality of meat products. Diet composition has been also demonstrated to influence the gene expression with effect on biological processes and pathways. However, the knowledge on the effect of nutrients at the molecular level is scant. In particular, studies on the effects of antioxidants and polyphenols dietary supplementation have been investigated mainly in rodents, and only scarcely in farm animals so far. RNA-Seq with next-generation sequencing is increasingly the method of choice for studying changes in the transcriptome and it has been recently employed also in pig nutrigenomics studies to identify diet-induced changes in gene expression. The present study aimed to investigate the effect of diets enriched with functional ingredients (linseed, vitamin E and plant extracts) on the transcriptome of pig Longissimus thoracis to elucidate the role of these compounds in influencing genes involved in muscle physiology and metabolism compared to a standard diet. RESULTS: Eight hundred ninety-three significant differentially expressed genes (DEGs) (FDR adjusted P-value ≤ 0.05) were detected by RNA-Seq analysis in the three diet comparisons (D2-D1, D3-D1, D4-D1). The functional analysis of DEGs showed that the diet enriched with n-3 PUFA from linseed (D2) mostly downregulated genes in pathways and biological processes (BPs) related to muscle development, contraction, and glycogen metabolism compared to the standard diet. The diet supplemented with linseed and vitamin E/Selenium (D3) showed to mostly downregulate genes linked to oxidative phosphorylation. Only few genes involved in extracellular matrix (ECM) organization were upregulated by the D3. Finally, the comparison D4-D1 showed that the diet supplemented with linseed and plant extracts (D4) upregulated the majority of genes compared to D1 that were involved in a complex network of pathways and BPs all connected by hub genes. In particular, IGF2 was a hub gene connecting protein metabolism, ECM organization, immune system and lipid biosynthesis pathways. CONCLUSION: The supplementation of pig diet with n-3 PUFA from linseed, antioxidants and plant-derived polyphenols can influence the expression of a relevant number of genes in Longissimus thoracis muscle that are involved in a variety of biochemical pathways linked to muscle function and metabolism.
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It remains incompletely understood whether there is an association between the transcriptome profiles of skeletal muscle and blood leukocytes in response to exercise or other physiological stressors. We have previously analyzed the changes in the muscle and blood neutrophil transcriptome in eight trained men before and 3, 48, and 96 h after 2 h cycling and running. Because we collected muscle and blood in the same individuals and under the same conditions, we were able to directly compare gene expression between the muscle and blood neutrophils. Applying weighted gene coexpression network analysis (WGCNA) as an advanced network-driven method to these original data sets enabled us to compare the muscle and neutrophil transcriptomes in a rigorous and systematic manner. Two gene networks were identified that were preserved between skeletal muscle and blood neutrophils, functionally related to mitochondria and posttranslational processes. Strong preservation measures (Zsummary > 10) for both muscle-neutrophil gene networks were evident within the postexercise recovery period. Muscle and neutrophil gene coexpression was strongly correlated in the mitochondria-related network (r = 0.97; P = 3.17E-2). We also identified multiple correlations between muscular gene subnetworks and exercise-induced changes in blood leukocyte counts, inflammation, and muscle damage markers. These data reveal previously unidentified gene coexpression between skeletal muscle and blood neutrophils following exercise, showing the value of WGCNA to understand exercise physiology. Furthermore, these findings provide preliminary evidence in support of the notion that blood neutrophil gene networks may potentially help us to track physiological and pathophysiological changes in the muscle.NEW & NOTEWORTHY By using weighted gene coexpression network analysis, an advanced bioinformatics method, we have identified previously unknown, functional gene networks that are preserved between skeletal muscle and blood neutrophils during recovery from exercise. These novel preliminary data suggest that muscular gene networks are coexpressed in blood leukocytes following physiological stress. This is a step forward toward the development of blood neutrophil gene subnetworks as part of blood biomarker panels to assess muscle health and disease.
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Biomarcadores/sangre , Ejercicio Físico/fisiología , Redes Reguladoras de Genes/fisiología , Músculo Esquelético/fisiología , Neutrófilos/fisiología , Resistencia Física/fisiología , Adulto , Humanos , Inflamación/fisiopatología , Recuento de Leucocitos/métodos , Masculino , Carrera/fisiología , Estrés Fisiológico/fisiología , Transcriptoma/fisiologíaRESUMEN
BACKGROUND: MicroRNAs (miRs) are small non-coding RNAs that regulate gene (mRNA) expression. Although the pathological role of miRs have been studied in muscle wasting conditions such as myotonic and muscular dystrophy, their roles in cancer cachexia (CC) are still emerging. OBJECTIVES: The objectives are (i) to profile human skeletal muscle expressed miRs; (ii) to identify differentially expressed (DE) miRs between cachectic and non-cachectic cancer patients; (iii) to identify mRNA targets for the DE miRs to gain mechanistic insights; and (iv) to investigate if miRs show potential prognostic and predictive value. METHODS: Study subjects were classified based on the international consensus diagnostic criteria for CC. Forty-two cancer patients were included, of which 22 were cachectic cases and 20 were non-cachectic cancer controls. Total RNA isolated from muscle biopsies were subjected to next-generation sequencing. RESULTS: A total of 777 miRs were profiled, and 82 miRs with read counts of ≥5 in 80% of samples were retained for analysis. We identified eight DE miRs (up-regulated, fold change of ≥1.4 at P < 0.05). A total of 191 potential mRNA targets were identified for the DE miRs using previously described human skeletal muscle mRNA expression data (n = 90), and a majority of them were also confirmed in an independent mRNA transcriptome dataset. Ingenuity pathway analysis identified pathways related to myogenesis and inflammation. qRT-PCR analysis of representative miRs showed similar direction of effect (P < 0.05), as observed in next-generation sequencing. The identified miRs also showed prognostic and predictive value. CONCLUSIONS: In all, we identified eight novel miRs associated with CC.
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MicroARNs/genética , Músculo Esquelético/metabolismo , ARN Mensajero/genética , Transcriptoma , Adulto , Anciano , Anciano de 80 o más Años , Caquexia/diagnóstico , Caquexia/etiología , Caquexia/metabolismo , Caquexia/mortalidad , Biología Computacional/métodos , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Anotación de Secuencia Molecular , Músculo Esquelético/patología , Neoplasias/complicaciones , Pronóstico , Interferencia de ARN , Reproducibilidad de los Resultados , Transducción de Señal , Tomografía Computarizada por Rayos XRESUMEN
Electrical activity is an important regulator of cellular function and gene expression in electrically excitable cell types. In the weakly electric teleost fish Sternopygus macrurus, electrocytes, i.e., the current-producing cells of the electric organ, derive from a striated muscle lineage. Mature electrocytes are larger than muscle fibers, do not contain sarcomeres, and are driven continuously at frequencies higher than those exerted on muscle cells. Previous work showed that the removal of electrical activity by spinal cord transection (ST) for two and five weeks led to an upregulation of some sarcomeric proteins and a decrease in electrocyte size. To test whether changes in gene transcription preceded these phenotypic changes, we determined the sensitivity of electrocyte gene expression to electrical inactivity periods of two and five days after ST. Whole tissue gene expression profiles using deep RNA sequencing showed minimal alterations in the levels of myogenic transcription factor and sarcomeric transcripts after either ST period. Moreover, while analysis of differentially expressed genes showed a transient upregulation of genes associated with proteolytic mechanisms at two days and an increase in mRNA levels of cytoskeletal genes at five days after electrical silencing, electrocyte size was not affected. Electrical inactivity also resulted in the downregulation of genes that were classified into enriched clusters associated with functions of axon migration and synapse structure. Overall, these data demonstrate that unlike tissues in the myogenic lineage in other vertebrate species, regulation of gene transcription and cell size in the muscle-like electrocytes of S. macrurus is highly insensitive to short-term electrical inactivity. Moreover, together with data obtained from control and long-term ST studies, the present data suggest that neural input might influence post-transcriptional processes to affect the mature electrocyte phenotype.
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Órgano Eléctrico/fisiología , Gymnotiformes/fisiología , Transcriptoma , Animales , Tamaño de la Célula , Órgano Eléctrico/citología , Gymnotiformes/genéticaRESUMEN
Skeletal muscle is distinguished from other tissues on the basis of its shape, biochemistry, and physiological function. Based on mammalian studies, fiber size, fiber types, and gene expression profiles are regulated, in part, by the electrical activity exerted by the nervous system. To address whether similar adaptations to changes in electrical activity in skeletal muscle occur in teleosts, we studied these phenotypic properties of ventral muscle in the electric fish Sternopygus macrurus following 2 and 5 days of electrical inactivation by spinal transection. Our data show that morphological and biochemical properties of skeletal muscle remained largely unchanged after these treatments. Specifically, the distribution of type I and type II muscle fibers and the cross-sectional areas of these fiber types observed in control fish remained unaltered after each spinal transection survival period. This response to electrical inactivation was generally reflected at the transcript level in real-time PCR and RNA-seq data by showing little effect on the transcript levels of genes associated with muscle fiber type differentiation and plasticity, the sarcomere complex, and pathways implicated in the regulation of muscle fiber size. Data from this first study characterizing the acute influence of neural activity on muscle mass and sarcomere gene expression in a teleost are discussed in the context of comparative studies in mammalian model systems and vertebrate species from different lineages.
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Fibras Musculares Esqueléticas/fisiología , Animales , Diferenciación Celular/fisiología , Peces , Transcriptoma/fisiologíaRESUMEN
Our objectives for this study were to understand the biological basis of meat tenderness and to provide an overview of the gene expression profiles related to meat quality as a tool for selection. Through deep mRNA sequencing, we analyzed gene expression in muscle tissues of two Italian cattle breeds: Maremmana and Chianina. We uncovered several differentially expressed genes that encode for proteins belonging to a family of tripartite motif proteins, which are involved in growth, cell differentiation and apoptosis, such as TRIM45, or play an essential role in regulating skeletal muscle differentiation and the regeneration of adult skeletal muscle, such as TRIM32. Other differentially expressed genes (SCN2B, SLC9A7 and KCNK3) emphasize the involvement of potassium-sodium pumps in tender meat. By mapping splice junctions in RNA-Seq reads, we found significant differences in gene isoform expression levels. The PRKAG3 gene, which is involved in the regulation of energy metabolism, showed four isoforms that were differentially expressed. This distinct pattern of PRKAG3 gene expression could indicate impaired glycogen storage in skeletal muscle, and consequently, this gene very likely has a role in the tenderization process. Furthermore, with this deep RNA-sequencing, we captured a high number of expressed SNPs, for example, we found 1462 homozygous SNPs showing the alternative allele with a 100% frequency when comparing tender and tough meat. SNPs were then classified into categories by their position and also by their effect on gene coding (174 non-synonymous polymorphisms) based on the available UMD_3.1 annotations.
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Cruzamiento , Bovinos/genética , Carne/análisis , Proteínas Musculares/genética , Transcriptoma , Proteínas Quinasas Activadas por AMP/genética , Alelos , Empalme Alternativo , Animales , Secuenciación de Nucleótidos de Alto Rendimiento , Italia , Músculo Esquelético/fisiología , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Análisis de Secuencia de ARNRESUMEN
The red cusk-eel (Genypterus chilensis) is an endemic fish species distributed along the coasts of the Eastern South Pacific. Biological studies on this fish are scarce, and genomic information for G. chilensis is practically non-existent. Thus, transcriptome information for this species is an essential resource that will greatly enrich molecular information and benefit future studies of red cusk-eel biology. In this work, we obtained transcriptome information of G. chilensis using the Illumina platform. The RNA sequencing generated 66,307,362 and 59,925,554 paired-end reads from skeletal muscle and liver tissues, respectively. De novo assembly using the CLC Genomic Workbench version 7.0.3 produced 48,480 contigs and created a reference transcriptome with a N50 of 846bp and average read coverage of 28.3×. By sequence similarity search for known proteins, a total of 21,272 (43.9%) contigs were annotated for their function. Out of these annotated contigs, 33.5% GO annotation results for biological processes, 32.6% GO annotation results for cellular components and 34.5% GO annotation results for molecular functions. This dataset represents the first transcriptomic resource for the red cusk-eel and for a member of the Ophidiimorpharia taxon.
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Peces/genética , Transcriptoma/genética , Animales , Secuencia de Bases , Biología Computacional , Cartilla de ADN/genética , ADN Complementario/genética , Perfilación de la Expresión Génica , Hígado/metabolismo , Anotación de Secuencia Molecular , Datos de Secuencia Molecular , Músculo Esquelético/metabolismo , Océano Pacífico , Análisis de Secuencia de ARNRESUMEN
We sought to ascertain the time course of transcriptional events that occur in human skeletal muscle at the outset of resistance exercise (RE) training in RE naive individuals and determine whether the magnitude of response was associated with exercise-induced muscle damage. Sixteen RE naive men were recruited; eight underwent two sessions of 5 × 30 maximum isokinetic knee extensions (180°/s) separated by 48 h. Muscle biopsies of the vastus lateralis, obtained from different sites, were taken at baseline and 24 h after each exercise bout. Eight individuals acted as nonexercise controls with biopsies obtained at the same time intervals. Transcriptional changes were assessed by microarray and protein levels of heat shock protein (HSP) 27 and αB-crystallin in muscle cross sections by immunohistochemistry as a proxy measure of muscle damage. In control subjects, no probe sets were significantly altered (false discovery rate < 0.05), and HSP27 and αB-crystallin protein remained unchanged throughout the study. In exercised subjects, significant intersubject variability following the initial RE bout was observed in the muscle transcriptome, with greatest changes occurring in subjects with elevated HSP27 and αB-crystallin protein. Following the second bout, the transcriptome response was more consistent, revealing a cohort of probe sets associated with immune activation, the suppression of oxidative metabolism, and ubiquitination, as differentially regulated. The results reveal that the initial transcriptional response to RE is variable in RE naive volunteers, potentially associated with muscle damage and unlikely to reflect longer term adaptations to RE training. These results highlight the importance of considering multiple time points when determining the transcriptional response to RE and associated physiological adaptation.