title: 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.transcriptome: sex differences, alternative splicing, and tissue homogeneity assessed with RNA sequencing.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden; malene.lindholm@ki.se.
authors.forename: Malene E
authors.initials: ME
authors.lastname: Lindholm
authors.affiliation: Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden; and.
authors.forename: Mikael
authors.initials: M
authors.lastname: Huss
authors.affiliation: Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology, Solna, Sweden.
authors.forename: Beata W
authors.initials: BW
authors.lastname: Solnestam
authors.affiliation: Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden; and.
authors.forename: Sanela
authors.initials: S
authors.lastname: Kjellqvist
authors.affiliation: Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology, Solna, Sweden.
authors.forename: Joakim
authors.initials: J
authors.lastname: Lundeberg
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden;
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Sundberg
mesh_terms: D000328:Adult; D017398:Alternative Splicing; D005260:Female; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D009928:Organ Specificity; D017423:Sequence Analysis, RNA; D012737:Sex Factors; D059467:Transcriptome
keywords: biopsy; gene expression profiling; isoform; novel transcript; splice variant