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. 2021 Apr 20;12:673404. doi: 10.3389/fphys.2021.673404

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Copyright © 2021 Theret, Rossi and Contreras.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Fibro-adipogenic progenitors are essential and required for efficient skeletal muscle regeneration and homeostatic neuromuscular integrity. Skeletal muscle FAPs are abundant stromal cells, reside within the connective tissue, and lie near the nerve parenchyma and NMJs in healthy muscles and homeostatic conditions. Conditional ablation of FAP+ cells using diphtheria toxin resulted in delayed regeneration and reduced numbers of MuSCs and HCs. In homeostasis and non-damaged muscles, widespread ablation of FAPs causes muscle atrophy, impair Schwann cell, and MuSC behavior and abundance. Impaired NMJ architecture and partial and complete muscle denervation also result from FAP cell ablation without damage. MuSC, muscle stem cell; HCs, hematopoietic cells; NMJ, neuromuscular junction. Motoneuron and Schwann cells are not shown in the middle panel because of space constraints and improved readability.