Fibro-adipogenic progenitors in skeletal muscle homeostasis, regeneration and diseases

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.

The effect of ageing on fat infiltration of thigh and paraspinal muscles in men

“…FAP cells can differentiate towards the fibrocyte and the adipocyte pathways [ 38 ] and have been shown to be crucial components of muscle regeneration [ 39 ]. However, they may also be an origin of fibrotic and fatty infiltration in pathology [ 40 ]. ICMLs, lipid droplets (LD) as ubiquitous cellular organelles, provide sources of energy and contribute to the effects of exercise on hypertrophy but also to many other cellular functions like the constitution of the cytoskeletal system and mitochondrial activity [ 41 ].…”

Exercise Induced-Cytokines Response in Marathon Runners: Role of ACE I/D and BDKRB2 +9/-9 Polymorphisms

“…Herein, we demonstrated greater IL-10 response and higher levels of BDNF in runners with -9 allele. IL-10 is the mainly antiinflammatory mediator that triggers the swift of M1 to M2, which is crucial to modulate the differentiation and fusion of myogenic cells on muscle regeneration (Molina et al, 2021). BDNF is an abundant neurotrophic factor produced and released by brain and skeletal muscle in response to exercise (Neeper et al, 1995;Wang et al, 2019) and the cellular sources of BDNF include muscle fiber type II, satellites cells and endothelial cells of skeletal muscle (Matthews et al, 2009;Rasmussen et al, 2009;Delezie et al, 2019;Di Rosa et al, 2021;Cefis et al, 2022).…”

Mesenchymal stem/stromal cells in the pathogenesis and regenerative therapy of inflammatory bowel diseases

“…In recent years, accumulating evidence has highlighted the important role of resident MSCs in the establishment of a unique tissue niche that is essential for tissue and immune homeostasis, while the dysregulated MSCs might contribute to the development of various pathological conditions ( 15 – 17 , 19 , 21 ). Similarly, recent studies have also implicated the importance of intestinal MSCs in digestive organ development, mucosal tissue, and immune homeostasis, which can provide multiple niche signals to support functional integration of mucosal epithelial cells, immune cells, and gut microbiota ( 37 – 39 ).…”

“…Given their wide existence in almost all tissues and organs of the body and their multifaceted biological functions, MSCs have been implicated to play essential roles in tissue homeostasis, regeneration, and diseases ( 15 – 19 ). Under physiological conditions, they may play an essential role in development, organogenesis, and maintenance of tissue and immune homeostasis through their cross-talks with specialized tissue cells and resident immune cells ( 15 , 18 , 19 ).…”

“…Given their wide existence in almost all tissues and organs of the body and their multifaceted biological functions, MSCs have been implicated to play essential roles in tissue homeostasis, regeneration, and diseases ( 15 – 19 ). Under physiological conditions, they may play an essential role in development, organogenesis, and maintenance of tissue and immune homeostasis through their cross-talks with specialized tissue cells and resident immune cells ( 15 , 18 , 19 ). On the other hand, in response to various insult signals, resident or endogenous MSCs may act as sensors of various insult signals and become activated by secreting a myriad of bioactive mediators that can foster or temper the immune/inflammatory responses, leading to the establishment of a pro-reparatory or regenerative microenvironment ( 20 ).…”