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

Rubenstein, A. B.; Smith, G. R.; Zhang, Z.; Chen, X.; Chambers, T. L.; Ruf-Zamojski, F.; Mendelev, N.; Cheng, W. S.; Zamojski, M.; Amper, M. A. S.; Nair, V. D.; Marderstein, A. R.; Montgomery, S. B.; Troyanskaya, O. G.; Zaslavsky, E.; Trappe, T.; Trappe, S.; Sealfon, S. C.

doi:10.1101/2023.09.26.558914

bioRxiv · 10.1101/2023.09.26.558914

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

Rubenstein, A. B.·Smith, G. R.·Zhang, Z.·Chen, X.·Chambers, T. L.·Ruf-Zamojski, F.·Mendelev, N.·Cheng, W. S.·Zamojski, M.·Amper, M. A. S.·Nair, V. D.·Marderstein, A. R.·Montgomery, S. B.·Troyanskaya, O. G.·Zaslavsky, E.·Trappe, T.·Trappe, S.·Sealfon, S. C.

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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 (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 as LUM-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.

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Rubenstein, A. B., Smith, G. R., Zhang, Z., Chen, X., Chambers, T. L., Ruf-Zamojski, F., Mendelev, N., Cheng, W. S., Zamojski, M., Amper, M. A. S., Nair, V. D., Marderstein, A. R., Montgomery, S. B., Troyanskaya, O. G., Zaslavsky, E., Trappe, T., Trappe, S., Sealfon, S. C.. 2023-09-28. Integrated single-cell multiome analysis reveals muscle fiber-type gene regulatory circuitry modulated by endurance exercise. https://doi.org/10.1101/2023.09.26.558914

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