Project description:Morphological studies of skeletal muscle tissue have provided detailed insights into the architecture of muscle fibers, the surrounding cells, and the extracellular matrix. However, a spatial proteomics analysis of the skeletal muscle, including the muscle-tendon transition zone, is lacking. Here, we prepared thin cryotome muscle sections along the longitudinal axis of the mouse soleus muscle and measured each muscle slice using short LC-MS gradients. We generated more than 3000 high-resolution longitudinal protein profiles of central to distal skeletal muscle regions and created a molecular network of different skeletal muscle regions that reveals the complex architecture of the muscle-tendon transition zone. Among the proteins that show an increasing profile from muscle to tendon, we find proteins related to neuronal activity, fatty acid biosynthesis, and the renin-angiotensin system (RAS). Blocking the RAS in cultured mouse tenocytes using losartan reduces the synthesis of extracellular matrix proteins, including collagen and fibronectin. Overall, our analysis of thin cryotome sections provides a spatial proteome of skeletal muscle and reveals that the RAS acts as an additional regulator of the matrix within muscle-tendon junctions.
Project description:Purpose: The main goal of this study is to compare skeletal muscle transcriptome profilings derived from sarcopenic versus healthy subjects. Methods: We use high coverage RNA sequencing of human skeletal muscle biopsies to analyze genome-wide transcriptional changes in human sarcopenia benchmarked to healthy elderly controls. Results: Muscle transcriptomic profiles demonstrate a prominent signature of mitochondrial dysfunction in sarcopenic patients. Conclusions: Our study supports the fundamental role of mitochondrial dysfunction in driving pathological muscle and mobility decline in the elderly.
Project description:The skeletal muscle system plays an important role in the independence of older adults. In this study we examine differences in the skeletal muscle transcriptome between healthy young and older subjects and (pre‐)frail older adults. Additionally, we examine the effect of resistance‐type exercise training on the muscle transcriptome in healthy older subjects and (pre‐)frail older adults. Baseline transcriptome profiles were measured in muscle biopsies collected from 53 young, 73 healthy older subjects, and 61 frail older subjects. Follow‐up samples from these frail older subjects (31 samples) and healthy older subjects (41 samples) were collected after 6 months of progressive resistance‐type exercise training. Frail older subjects trained twice per week and the healthy older subjects trained three times per week. At baseline genes related to mitochondrial function and energy metabolism were differentially expressed between older and young subjects, as well as between healthy and frail older subjects. Three hundred seven genes were differentially expressed after training in both groups. Training affected expression levels of genes related to extracellular matrix, glucose metabolism, and vascularization. Expression of genes that were modulated by exercise training was indicative of muscle strength at baseline. Genes that strongly correlated with strength belonged to the protocadherin gamma gene cluster (r = −0.73). Our data suggest significant remaining plasticity of ageing skeletal muscle to adapt to resistance‐type exercise training. Some age‐related changes in skeletal muscle gene expression appear to be partially reversed by prolonged resistance‐type exercise training. The protocadherin gamma gene cluster may be related to muscle denervation and re‐innervation in ageing muscle.
Project description:Human skeletal muscle cell cultures (HSkMC) were exposed to particles of various tungsten alloys or tantalum and transcriptomic responses after 24 hours were determined by gene expression microarrays in comparison with untreated control cultures.
Project description:Human skeletal muscle cell cultures (HSkMC) were exposed to particles of various tungsten alloys or tantalum and transcriptomic responses after 24 hours were determined by gene expression microarrays in comparison with untreated control cultures.
Project description:To elucidate the epithelial cell diversity within the nasal inferior turbinates, a comprehensive investigation was conducted comparing control subjects to individuals with house dust mite-induced allergic rhinitis. This study aimed to delineate the differential expression profiles and phenotypic variations of epithelial cells in response to allergic rhinitis. This research elucidated distinct subpopulations and rare cell types of epithelial cells within the nasal turbinates, discerning alterations induced by allergic rhinitis. Furthermore, by interrogating transcriptomic signatures, the investigation provided novel insights into the cellular dynamics and immune responses underlying allergic rhinitis pathogenesis
Project description:Forkhead box class O (FoxO) transcription factors regulate whole body energy metabolism, skeletal muscle mass and substrate switching. To elucidate the role of FOXO in skeletal muscle, dominant negative (dn) constructs for FOXO1 (FOXO1dn) or FOXO3 (FOXO3dn) were transfected by electroporation into mouse tibialis anterior muscle and glucose uptake, signal transduction, and glucose stimulated gene expression profiles were assessed. Results were compared against contralateral control transfected muscle. Transcriptomic analysis revealed major pathways affected by FOXO1dn or FOXO3dn revolve around metabolism and inflammation.
Project description:The few investigations on exercise-induced global gene expression responses in human skeletal muscle haves typically focused at one specific mode of exercise and few such studies have implemented control measures. However, interpretation on distinct phenotype regulation necessitate comparison between essentially different modes of exercise and the ability to identify true exercise effects, necessitate implementation of independent non-exercise control subjects. Furthermore, muscle transkriptometranscriptome data made available through previous exercise studies can be difficult to extract and interpret by individuals that are inexperienced with bioinformatic procedures. In a comparative study, we; (1) investigated the human skeletal muscle transcriptome response to differentiated exercise and non-exercise control intervention, and; (2) aimed to develop a straightforward search tool to allow for easy extraction and interpretation of our data. We provide a simple spreadsheet containing transcriptome data allowing other investigators to see how mRNA of their interest behave in skeletal muscle following exercise, both endurance, strength and non-exercise. Our approach, allow investigators easy access to information on genuine transcriptome effects of differentiated exercise, to better aid hyporthesis-driven question in this particular field of research.