Macrophages are essential to muscle regeneration, as they regulate inflammation, carry out phagocytosis, and facilitate tissue repair. These cells exhibit phenotypic switching from pro-inflammatory (M1) to anti-inflammatory (M2) states during muscle repair, influencing myoblast proliferation, differentiation, and myofiber formation. In Duchenne Muscular Dystrophy (DMD), asynchronous muscle injuries disrupt the normal temporal stages of regeneration, leading to fibrosis and failed regeneration. Altered macrophage activity is associated with DMD progression and physiopathology. Gaining insight into the intricate relationship between macrophages and muscle cells is crucial for creating effective therapies aimed at treating this muscle disorder. This review explores the dynamic functions of macrophages in muscle regeneration and their implications in DMD.

The epicardium is the outermost cell layer in the vertebrate heart that originates during development from mesothelial precursors located in the proepicardium and septum transversum. The epicardial layer plays a key role during cardiogenesis since a subset of epicardial-derived cells (EPDCs) undergo an epithelial–mesenchymal transition (EMT); migrate into the myocardium; and differentiate into distinct cell types, such as coronary vascular smooth muscle cells, cardiac fibroblasts, endothelial cells, and presumably a subpopulation of cardiomyocytes, thus contributing to complete heart formation. Furthermore, the epicardium is a source of paracrine factors that support cardiac growth at the last stages of cardiogenesis. Although several lineage trace studies have provided some evidence about epicardial cell fate determination, the molecular mechanisms underlying epicardial cell heterogeneity remain not fully understood. Interestingly, seminal works during the last decade have pointed out that the adult epicardium is reactivated after heart damage, re-expressing some embryonic genes and contributing to cardiac remodeling. Therefore, the epicardium has been proposed as a potential target in the treatment of cardiovascular disease. In this review, we summarize the previous knowledge regarding the regulation of epicardial cell contribution during development and the control of epicardial reactivation in cardiac repair after damage.

The outermost layer of the heart, the epicardium, is an essential cell population that contributes, through epithelial-to-mesenchymal transition (EMT), to the formation of different cell types and provides paracrine signals to the developing heart. Despite its quiescent state during adulthood, the adult epicardium reactivates and recapitulates many aspects of embryonic cardiogenesis in response to cardiac injury, thereby supporting cardiac tissue remodeling. Thus, the epicardium has been considered a crucial source of cell progenitors that offers an important contribution to cardiac development and injured hearts. Although several studies have provided evidence regarding cell fate determination in the epicardium, to date, it is unclear whether epicardium-derived cells (EPDCs) come from specific, and predetermined, epicardial cell subpopulations or if they are derived from a common progenitor. In recent years, different approaches have been used to study cell heterogeneity within the epicardial layer using different experimental models. However, the data generated are still insufficient with respect to revealing the complexity of this epithelial layer. In this review, we summarize the previous works documenting the cellular composition, molecular signatures, and diversity within the developing and adult epicardium.

The outermost layer of the heart, the epicardium, is an essential cell population that contributes, through epithelial-to-mesenchymal transition (EMT), to form different cell types and provide paracrine signals to the developing heart. Despite its quiescent state during adulthood, in response to cardiac injury, adult epicardium reactivates and recapitulates many aspects of embryonic cardiogenesis supporting cardiac tissue remodeling. Thus, the epicardium has been considered as a crucial source of cell progenitors with important contribution to developing and injured heart. Although several studies have provided evidence about cell fate determination in the epicardium, to date it is unclear whether epicardial-derived cells (EPDCs) come from specific, and previously predetermined, epicardial cell subpopulations or if they are derived from a common progenitor. In recent years, different approaches have been used to study cell heterogeneity within the epicardial layer by using different experimental models. However, generated data are still insufficient to understand the complexity of this epithelial layer. In this review, we summarize the previous works supporting the cellular composition, molecular signatures and diversity within the developing and adult epicardium.