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

ABSTRACT: Endurance exercise is an important health modifier. We studied cell-type specific adaptations of human skeletal muscle to acute endurance exercise using single-nucleus multiome sequencing in human vastus lateralis samples collected before and 3.5 hours after 40 min exercise at 70% VO2 max in four subjects, as well as in matched time of day samples from two supine resting circadian controls. High quality same cell RNAseq and ATACseq 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. Comprehensive single cell regulatory circuit analysis identified distinct fiber type programs involving 272 TFs regulating 1579 genes at specific regulated chromatin sites, with fast fibers showing more robust circuit responses. These data and comprehensive circuit reconstruction provide a high resolution map of the molecular adaptations to exercise at single cell resolution.

ORGANISM(S): Homo sapiens

PROVIDER: GSE240061 | GEO | 2025/05/05

REPOSITORIES: GEO

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Project description:The molecular mechanisms of exercise-induced cardiovascular protection are poorly understood. There is growing evidence that reactive oxygen species (ROS) are necessary for some of these adaptations and antioxidants may be used to investigate this effect. This study aimed to determine the effects of exercise and/or antioxidant supplementation on myocardial and vascular endothelium gene expression. Male Wistar rats were divided into four groups: i) endurance exercise (90min of treadmill running 4d/week, 14 weeks); ii) antioxidant-treated; iii) antioxidant and endurance exercise and iv) control. The supplemented animals received Vitamin E (1000 IU/kg diet) and ï¡-lipoic acid (1.6 g/kg diet) mixed with rat chow. cDNA microarray analysis was performed using purified endothelial RNA from myocardial and coronary artery endothelial cells and showed that the expression levels of 35, 40 and 40 genes were altered for groups i, ii, and iii respectively compared to control. Differentially expressed genes were analysed using the KEGG pathway database, hierarchical cluster and DAVID analysis. These analyses revealed that a gene involved in cardiovascular disease progression, Ras homolog gene family member A (RhoA) was down-regulated by exercise, upregulated by antioxidant supplementation and the combination of exercise and antioxidant blunted both effects. These findings were confirmed by real-time PCR. In summary, exercise and antioxidant supplementation affect endothelial cell gene expression and ROS appear necessary for some of these adaptations. 48 Male Wistar rats were divided into four groups: i) endurance exercise (90min of treadmill running 4d/week, 14 weeks); ii) antioxidant-treated; iii) antioxidant and endurance exercise and iv) control. The supplemented animals received Vitamin E (1000 IU/kg diet) and ï¡-lipoic acid (1.6 g/kg diet) mixed with rat chow. cDNA microarray analysis was performed using purified endothelial RNA from myocardial and coronary artery endothelial cells. Based on the limited material available, it was necessary to combine the RNA into three pools per treatment group for CAEC (approx 400 ng of total RNA), and four pools for LVEC (approx 1 Î¼g of total RNA) with an additional reference pool from each control group.

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

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