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

• Published in: bioRxiv
• Main Authors: Rubenstein, Aliza B, Smith, Gregory R, Zhang, Zidong, Chen, Xi, Chambers, Toby L, Ruf-Zamojski, Frederique, Mendelev, Natalia, Cheng, Wan Sze, Zamojski, Michel, Amper, Mary Anne S, Nair, Venugopalan D, Marderstein, Andrew R, Montgomery, Stephen B, Troyanskaya, Olga G, Zaslavsky, Elena, Trappe, Todd, Trappe, Scott, Sealfon, Stuart C
• Format: Journal Article
• Language: English
• Published: United States 09.10.2023
• Subjects: acute endurance exercise; human vastus lateralis; single-nucleus multiome; circadian control; transcriptomics; epigenomics; gene regulatory circuits; skeletal muscle; snRNA-seq/snATAC-seq; PPARδ
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2023.09.26.558914

Endurance 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% VO max 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 as -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.