Abstract
Skeletal muscle possesses a remarkable regenerative capacity that relies on the activity of muscle stem cells, also known as satellite cells. The presence of non-myogenic cells also plays a key role in the coordination of skeletal muscle regeneration. Particularly, fibro-adipogenic progenitors (FAPs) emerged as master regulators of muscle stem cell function and skeletal muscle regeneration. This population of muscle resident mesenchymal stromal cells has been initially characterized based on its bi-potent ability to differentiate into fibroblasts or adipocytes. New technologies such as single-cell RNAseq revealed the cellular heterogeneity of FAPs and their complex regulatory network during muscle regeneration. In acute injury, FAPs rapidly enter the cell cycle and secrete trophic factors that support the myogenic activity of muscle stem cells. Conversely, deregulation of FAP cell activity is associated with the accumulation of fibrofatty tissue in pathological conditions such as muscular dystrophies and ageing. Considering their central role in skeletal muscle pathophysiology, the regulatory mechanisms of FAPs and their cellular and molecular crosstalk with muscle stem cells are highly investigated in the field. In this review, we summarize the current knowledge on FAP cell characteristics, heterogeneity and the cellular crosstalk during skeletal muscle homeostasis and regeneration. We further describe their role in muscular disorders, as well as different therapeutic strategies targeting these cells to restore muscle regeneration.
Highlights
With more than 600 skeletal muscles and accounting for 35–45% of the body mass, striated skeletal muscle is the most abundant tissue in the human body [1]
Odd skipped-related 1 (Osr1)+ fibro-adipogenic progenitors (FAPs) can be divided in two subgroups, the dipeptidyl peptidase-4 (Dpp4) positive and the chemokine (C–X–C motif ) ligand 4 (Cxcl4) positive cell populations indicating that they are re-acquiring cellular heterogeneity similar to what is observed in non-injured muscles [9,40]
Skeletal muscle has a remarkable regenerative capacity that has been attributed to the presence and activity of muscle stem cells
Summary
With more than 600 skeletal muscles and accounting for 35–45% of the body mass, striated skeletal muscle is the most abundant tissue in the human body [1]. Skeletal muscles play a role in vital functions, such as locomotion, breathing, thermoregulation, energy metabolism and endocrine signalling Considering their role in movement and exercise, skeletal muscles are subjected to various physical stresses and traumas. There is a rapid accumulation of immune cells (neutrophils, pro- and anti-inflammatory macrophages, natural killer cells, B- and T-cells) and changes in the proportion of nonimmune cells (endothelial cells, smooth muscle cells, glial cells, tenocytes and fibro-adipogenic progenitors). These different cell types provide molecular cues to guide muscle stem cells through myogenesis [5]. This review aims at summarizing the recent knowledge on FAP cell characteristics, cellular interactions and roles in skeletal muscle under physiological and pathological conditions
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