Project description:To investigate the molecular mechanisms governing the transition of skeletal muscle from atrophy to compensatory regeneration and hypertrophy, we employed a mouse model involving hindlimb unloading and subsequent reloading, conducting a comprehensive analysis of global gene expression using RNA-sequencing (RNA-seq). Gastrocnemius muscle samples were obtained from three groups: control mice, mice subjected to 10 days of hindlimb unloading-induced muscle atrophy, and mice reintroduced to normal cage activity for 1 day following the unloading period (reloading).
Project description:To uncover novel genes and molecular pathways important for skeletal muscle remodeling and regeneration, we used a mouse hindlimb unloading and reloading protocol. We then performed analysis of global gene expression by RNA-sequencing (RNA-seq), looking at the transition from muscle unloading to reloading (GSE237099). This study focuses on the microprotein Mustn1 (Musculoskeletal embryonic nuclear protein 1, also known as Mustang), which consists of 82 amino acids. We performed RNA-sequencing of soleus muscle from 8-week-old mice carrying one allele (heterozygous) of Mustn1 tm1a (KO-first) and wildtype littermates.
Project description:Rodent hind limb unloading was used as a model for reduced muscle activity and eventual atrophy. After a 10 day period of unloading, mice in this study were “reloaded” for 3 days and regained use of their hind limbs. We report the application of Next-generation sequencing (NGS) technology for high-throughput profiling of mRNA in soleus muscle of adult (6 mo) and aged (22-24 mo) mice. Our goal was to determine the effects of hind limb unloading and reloading on mRNA profiles in soleus muscle and compare between adult and aged mice. We find that there are distinct response in the profile of fatty acid oxidation, TCA cycle, ETC oxidative phosphorylation gene expression patterns in response to unloading and reloading. The repsonses are generally simialr between young and old mice.
Project description:It is unknown if adult human skeletal muscle has an epigenetic memory of earlier encounters with growth. We report, for the first time in humans, genome-wide DNA methylation (850,000CpGs) and gene expression analysis after muscle hypertrophy (loading), return of muscle mass to baseline (unloading), followed by later hypertrophy (reloading). We discovered increased frequency of hypomethylation across the genome after reloading (18,816 CpGs) versus earlier loading (9,153 CpG sites). We also identified AXIN1, GRIK2, CAMK4, TRAF1 as hypomethylated genes with enhanced expression after loading that maintained their hypomethylated status even during unloading where muscle mass returned to control levels, indicating a memory of these genes methylation signatures following earlier hypertrophy. Further, UBR5, RPL35a, HEG1, PLA2G16, SETD3 displayed hypomethylation and enhanced gene expression following loading, and demonstrated the largest increases in hypomethylation, gene expression and muscle mass after later reloading, indicating an epigenetic memory in these genes. Finally, genes; GRIK2, TRAF1, BICC1, STAG1 were epigenetically sensitive genes demonstrating hypomethylation after a single bout of resistance exercise that was maintained 22 weeks later with the largest increase in gene expression and muscle mass after reloading. Overall, we identify an important epigenetic role for a number of largely unstudied genes in muscle hypertrophy/ memory.
Project description:Skeletal muscle is a highly adaptive tissue that changes with many physiological stimuli and is composed of many cell types. Upon muscle injury, the concerted action of these cells is required to proceed through the process of inflammation, extracellular matrix remodeling, and restoration of function. To uncover novel genes and molecular pathways important for skeletal muscle remodeling and regeneration, we used a mouse hindlimb unloading and reloading protocol, and performed transcriptomics analysis. This study focuses on the microprotein Mustn1 (Musculoskeletal embryonic nuclear protein 1, also known as Mustang), whose gene expression is increased in muscle at the onset of hindlimb reloading, exercise, and injury. We generated a whole-body Mustn1 knockout mouse model and performed proteomics analysis of muscle and aorta.
Project description:Spaceflight results in a number of adaptations to skeletal muscle, including atrophy and shifts towards faster muscle fiber types. To identify changes in gene expression that may underlie these adaptations, microarray expression analysis was performed on gastrocnemius from mice flown on the STS-108 shuttle flight (11 days, 19 hours) versus mice maintained on earth for the same period. Additionally, to identify changes that were due to unloading and reloading, microarray analyses were conducted on calf muscle from ground-based mice subjected to hindlimb suspension (12 days) and mice subjected to hindlimb suspension plus a brief period of reloading (3.5 hours) to simulate the time between landing and sacrifice of the spaceflight mice.
Project description:Few studies have assessed the patterns of parasite populations of rodents over a longitudinal gradient in Chile. In this work, the gastrointestinal helminthic fauna of invasive rodents in Chile was examined to assess the association between their presence/absence and abundance with latitude, host sex, and host body condition, and to assess the coexistence and correlation of the abundance between parasite species. Rodents were obtained from 20 localities between 33 and 43°S. Helminths were extracted from the gastrointestinal tract and identified morphologically. Overall, 13 helminth taxa were obtained. The most frequently identified parasite species was Heterakis spumosa, and the most abundant was Syphacia muris, while Physaloptera sp. was the most widely distributed. No locality presented with a coexistence that was different from that expected by chance, while the abundance of five helminthic species correlated with the abundance of another in at least one locality, most likely due to co-infection rather than interaction. Host sex was associated with parasite presence or abundance, and female sex-biased parasitism was notably observed in all cases. Body condition and latitude presented either a positive or negative association with the presence or abundance of parasites depending on the species. It is notable that the likely native Physaloptera sp. is widely distributed among invasive rodents. Further, gravid females were found, suggesting spillback of this species to the native fauna. The low frequency and abundance of highly zoonotic hymenolepid species suggest that rodents are of low concern regarding gastrointestinal zoonotic helminths.