Cellular deconstruction of the human skeletal muscle microenvironment identifies an exercise-induced histaminergic crosstalk
- Author
- Thibaux Van der Stede (UGent) , Alexia Van de Loock (UGent) , Guillermo Turiel, Camilla Hansen, Andrea Tamariz-Ellemann, Max Ullrich (UGent) , Eline Lievens (UGent) , Jan Spaas, Nurten Yigit (UGent) , Jasper Anckaert (UGent) , Justine Nuytens (UGent) , Siegrid De Baere (UGent) , Ruud Van Thienen (UGent) , Anneleen Weyns (UGent) , Laurie De Wilde (UGent) , Peter Van Eenoo (UGent) , Siska Croubels (UGent) , John R. Halliwill, Pieter Mestdagh (UGent) , Erik A. Richter, Lasse Gliemann, Ylva Hellsten, Jo Vandesompele (UGent) , Katrien De Bock and Wim Derave (UGent)
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- Abstract
- Plasticity of skeletal muscle is induced by transcriptional and translational events in response to exercise, leading to multiple health and performance benefits. The skeletal muscle microenvironment harbors myofibers and mononuclear cells, but the rich cell diversity has been largely ignored in relation to exercise adaptations. Using our workflow of transcriptome profiling of individual myofibers, we observed that their exerciseinduced transcriptional response was surprisingly modest compared with the bulk muscle tissue response. Through the integration of single-cell data, we identified a small mast cell population likely responsible for histamine secretion during exercise and for targeting myeloid and vascular cells rather than myofibers. We demonstrated through histamine H1 or H2 receptor blockade in humans that this paracrine histamine signaling cascade drives muscle glycogen resynthesis and coordinates the transcriptional exercise response. Altogether, our cellular deconstruction of the human skeletal muscle microenvironment uncovers a histamine-driven intercellular communication network steering muscle recovery and adaptation to exercise
- Keywords
- Cellular deconstruction, Cellular deconstruction human skeletal muscle, human skeletal muscle, human skeletal muscle microenvironment, exercise-induced histaminergic crosstalk, histaminergic crosstalk, HISTIDINE-DECARBOXYLASE, MESSENGER-RNA, INCREASES, INSULIN, CELLS, H-1, PHARMACOKINETICS, VASODILATION, REGENERATION, CONTRIBUTES
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Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01JMH6QTBXHTYVR2YWBJKTTZNQ
- MLA
- Van der Stede, Thibaux, et al. “Cellular Deconstruction of the Human Skeletal Muscle Microenvironment Identifies an Exercise-Induced Histaminergic Crosstalk.” CELL METABOLISM, vol. 37, no. 4, 2025, pp. 842-856.e7, doi:10.1016/j.cmet.2024.12.011.
- APA
- Van der Stede, T., Van de Loock, A., Turiel, G., Hansen, C., Tamariz-Ellemann, A., Ullrich, M., … Derave, W. (2025). Cellular deconstruction of the human skeletal muscle microenvironment identifies an exercise-induced histaminergic crosstalk. CELL METABOLISM, 37(4), 842-856.e7. https://doi.org/10.1016/j.cmet.2024.12.011
- Chicago author-date
- Van der Stede, Thibaux, Alexia Van de Loock, Guillermo Turiel, Camilla Hansen, Andrea Tamariz-Ellemann, Max Ullrich, Eline Lievens, et al. 2025. “Cellular Deconstruction of the Human Skeletal Muscle Microenvironment Identifies an Exercise-Induced Histaminergic Crosstalk.” CELL METABOLISM 37 (4): 842-856.e7. https://doi.org/10.1016/j.cmet.2024.12.011.
- Chicago author-date (all authors)
- Van der Stede, Thibaux, Alexia Van de Loock, Guillermo Turiel, Camilla Hansen, Andrea Tamariz-Ellemann, Max Ullrich, Eline Lievens, Jan Spaas, Nurten Yigit, Jasper Anckaert, Justine Nuytens, Siegrid De Baere, Ruud Van Thienen, Anneleen Weyns, Laurie De Wilde, Peter Van Eenoo, Siska Croubels, John R. Halliwill, Pieter Mestdagh, Erik A. Richter, Lasse Gliemann, Ylva Hellsten, Jo Vandesompele, Katrien De Bock, and Wim Derave. 2025. “Cellular Deconstruction of the Human Skeletal Muscle Microenvironment Identifies an Exercise-Induced Histaminergic Crosstalk.” CELL METABOLISM 37 (4): 842-856.e7. doi:10.1016/j.cmet.2024.12.011.
- Vancouver
- 1.Van der Stede T, Van de Loock A, Turiel G, Hansen C, Tamariz-Ellemann A, Ullrich M, et al. Cellular deconstruction of the human skeletal muscle microenvironment identifies an exercise-induced histaminergic crosstalk. CELL METABOLISM. 2025;37(4):842-856.e7.
- IEEE
- [1]T. Van der Stede et al., “Cellular deconstruction of the human skeletal muscle microenvironment identifies an exercise-induced histaminergic crosstalk,” CELL METABOLISM, vol. 37, no. 4, pp. 842-856.e7, 2025.
@article{01JMH6QTBXHTYVR2YWBJKTTZNQ,
abstract = {{Plasticity of skeletal muscle is induced by transcriptional and translational events in response to exercise, leading to multiple health and performance benefits. The skeletal muscle microenvironment harbors myofibers and mononuclear cells, but the rich cell diversity has been largely ignored in relation to exercise adaptations. Using our workflow of transcriptome profiling of individual myofibers, we observed that their exerciseinduced transcriptional response was surprisingly modest compared with the bulk muscle tissue response.
Through the integration of single-cell data, we identified a small mast cell population likely responsible for histamine secretion during exercise and for targeting myeloid and vascular cells rather than myofibers. We
demonstrated through histamine H1 or H2 receptor blockade in humans that this paracrine histamine signaling cascade drives muscle glycogen resynthesis and coordinates the transcriptional exercise response. Altogether, our cellular deconstruction of the human skeletal muscle microenvironment uncovers a histamine-driven intercellular communication network steering muscle recovery and adaptation to exercise}},
author = {{Van der Stede, Thibaux and Van de Loock, Alexia and Turiel, Guillermo and Hansen, Camilla and Tamariz-Ellemann, Andrea and Ullrich, Max and Lievens, Eline and Spaas, Jan and Yigit, Nurten and Anckaert, Jasper and Nuytens, Justine and De Baere, Siegrid and Van Thienen, Ruud and Weyns, Anneleen and De Wilde, Laurie and Van Eenoo, Peter and Croubels, Siska and Halliwill, John R. and Mestdagh, Pieter and Richter, Erik A. and Gliemann, Lasse and Hellsten, Ylva and Vandesompele, Jo and De Bock, Katrien and Derave, Wim}},
issn = {{1550-4131}},
journal = {{CELL METABOLISM}},
keywords = {{Cellular deconstruction,Cellular deconstruction human skeletal muscle,human skeletal muscle,human skeletal muscle microenvironment,exercise-induced histaminergic crosstalk,histaminergic crosstalk,HISTIDINE-DECARBOXYLASE,MESSENGER-RNA,INCREASES,INSULIN,CELLS,H-1,PHARMACOKINETICS,VASODILATION,REGENERATION,CONTRIBUTES}},
language = {{eng}},
number = {{4}},
pages = {{842--856.e7}},
title = {{Cellular deconstruction of the human skeletal muscle microenvironment identifies an exercise-induced histaminergic crosstalk}},
url = {{http://doi.org/10.1016/j.cmet.2024.12.011}},
volume = {{37}},
year = {{2025}},
}
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