Extensive Differential Gene Expression and Regulation by Sex in Human Skeletal Muscle

Strategic Insights -

Researchers at the University of Michigan have discovered significant sex differences in gene expression and regulation in human skeletal muscle. Using bulk and single-nucleus RNA sequencing and single-nucleus ATAC-seq data from 281 skeletal muscle biopsies, the study found that over 2,100 genes showed highly concordant sex-biased expression across different muscle fiber types and bulk tissue. The findings highlight the importance of understanding sex-differential patterns of health and disease.

Key Takeaways:

  • The study found that over 2,100 genes showed highly concordant sex-biased expression across different muscle fiber types and bulk tissue.
  • Gene pathways related to mitochondrial activity and energy metabolism were enriched for male-biased expression, whereas those related to signal transduction and cell differentiation were enriched for female-biased expression.
  • Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) also showed extensive sex-biased expression in the fiber-type and bulk data, respectively.
  • The study identified widespread sex-biased chromatin accessibility enriched in proximal and distal gene regulatory states.
  • The researchers found that sex-biased chromatin accessibility in gene promoters was positively associated with sex-biased expression.
  • The findings highlight nuclear and cytoplasmic mechanisms for sex-differential gene regulation in skeletal muscle.
  • The study suggests that sex differences in gene expression and regulation may play a crucial role in understanding sex-differential patterns of health and disease.
  • Abigail S. Mauger, Department of Biostatistics and Center for Statistical Genetics, University of Michigan, was a lead researcher on the study.
  • Additional authors on the study include Sarah C. Hanks, Arushi Varshney, Dan L. Ciotlos, Nandini Manickam, Narisu Narisu, Alexandria J. Shumway, Peter Orchard, Michael R. Erdos, Michael D. Sweeney, Jeffrey Okamoto, Anne U. Jackson, Heather M. Stringham, Lori L. Bonnycastle.

Statistics:

  • 2,100 genes showed highly concordant sex-biased expression across different muscle fiber types and bulk tissue.
  • 281 skeletal muscle biopsies were used in the study.
  • Gene pathways related to mitochondrial activity and energy metabolism were enriched for male-biased expression.
  • Gene pathways related to signal transduction and cell differentiation were enriched for female-biased expression.
  • Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) showed extensive sex-biased expression in the fiber-type and bulk data, respectively.
  • 281 skeletal muscle biopsies were used in the study.

Sources:

  • Extensive differential gene expression and regulation by sex in human skeletal muscle. Cell Genomics, 2025;5(8):100915.
  • NewsRx. Studies from University of Michigan Yield New Data on Cell Genomics (Extensive differential gene expression and regulation by sex in human skeletal muscle). Biotech Week. September 17, 2025; p 2091.