The human skeletal muscle transcriptome: sex differences, alternative splicing, and tissue homogeneity assessed with RNA sequencing

Abstract

Human skeletal muscle health is important for quality of life and several chronic diseases, including type II diabetes, heart disease, and cancer. Skeletal muscle is a tissue widely used to study mechanisms behind different diseases and adaptive effects of controlled interventions. For such mechanistic studies, knowledge about the gene expression profiles in different states is essential. Since the baseline transcriptome has not been analyzed systematically, the purpose of this study was to provide a deep reference profile of female and male skeletal muscle. RNA sequencing data were analyzed from a large set of 45 resting human muscle biopsies. We provide extensive information on the skeletal muscle transcriptome, including 5 previously unannotated protein-coding transcripts. Global transcriptional tissue homogeneity was strikingly high, within both a specific muscle and the contralateral leg. We identified >23,000 known isoforms and found >5000 isoforms that differ between the sexes. The female and male transcriptome was enriched for genes associated with oxidative metabolism and protein catabolic processes, respectively. The data demonstrate remarkably high tissue homogeneity and provide a deep and extensive baseline reference for the human skeletal muscle transcriptome, with regard to alternative splicing, novel transcripts, and sex differences in functional ontology.-Lindholm, M. E., Huss, M., Solnestam, B. W., Kjellqvist, S., Lundeberg, J., Sundberg, C. J. The human skeletal muscle transcriptome: sex differences, alternative splicing, and tissue homogeneity assessed with RNA sequencing. FASEB J. 28, 4571-4581 (2014). www.fasebj.org

Transcriptome and Functional Profile of Cardiac Myocytes Is Influenced by Biological Sex

“…18, 35, 36 Similar to what we observed in cardiac myocytes, there are many genes that are differentially expressed between the sexes with modest fold-changes, however, the gene changes are highly tissue specific and are enriched for distinct signaling pathways. 35 Several previous reports have sought to describe sex differences in cardiac gene expression.…”

Humanin skeletal muscle protein levels increase after resistance training in men with impaired glucose metabolism

“…Thus potential gender differences has to be taken into account (Lindholm et al. ). Furthermore, baseline BMI differences between these two study populations might play a role, with this study population having a higher BMI than the population by Voigt & Jelinek.…”

“…In addition, our study only included males, whereas most subjects were females in the aforementioned study. Thus potential gender differences has to be taken into account (Lindholm et al 2014). Furthermore, baseline BMI differences between these two study populations might play a role, with this study population having a higher BMI than the population by Voigt & Jelinek. Increases in mitochondrial number and volume as well as biochemical changes within the mitochondria are wellestablished responses to aerobic exercise training (Howald et al 1985).…”

Differential response trajectories to acute exercise in blood and muscle

“…We were unable to identify any public transcriptome datasets for acute resistance exercise interventions in blood, where future research efforts are needed. At baseline, there are large sex differences in the human skeletal muscle transcriptome (Lindholm et al, 2014b;Maher et al, 2009) . However, there are only a few studies that have reported sex-differences in transcriptional regulation with exercise, and these have only looked at specific genes with qRT-PCR (Smith et al, 2009;Vissing et al, 2008) .…”