Integrated single-cell multiome analysis reveals muscle fiber-type gene regulatory circuitry modulated by endurance exercise

Abstract

SummaryEndurance exercise is an important health modifier. We studied cell-type specific adaptations of human skeletal muscle to acute endurance exercise using single-nucleus (sn) multiome sequencing in human vastus lateralis samples collected before and 3.5 hours after 40 min exercise at 70% VO2max in four subjects, as well as in matched time of day samples from two supine resting circadian controls. High quality same-cell RNA-seq and ATAC-seq data were obtained from 37,154 nuclei comprising 14 cell types. Among muscle fiber types, both shared and fiber-type specific regulatory programs were identified. Single-cell circuit analysis identified distinct adaptations in fast, slow and intermediate fibers as well asLUM-expressing FAP cells, involving a total of 328 transcription factors (TFs) acting at altered accessibility sites regulating 2,025 genes. These data and circuit mapping provide single-cell insight into the processes underlying tissue and metabolic remodeling responses to exercise.

Combined aerobic and resistance exercise training alters the spatial transcriptome of skeletal muscle in young adults

“…Previous high resolution single cell/nucleus sequencing and deconvolution of bulk muscle transcriptomics from human samples have detected approximately a dozen different cell types present in the muscle environment, varying by donor condition and clustering approach 10,12,24,25,28 . Here, unbiased clustering of spatial gene expression signatures identified 8 unique cell clusters, including two cluster groups that were uniquely modulated by chronic exercise training.…”