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Skeletal muscle is a terminally differentiated cell composed of multinucleated muscle fibers. Adult muscle fibers lose the ability to undergo mitosis, so skeletal muscle damage is mostly irreversible. Myosatellite cells are a type of adult stem cells that exist between the basement membrane and the sarcolemma of muscle cells. As myogenic stem cells, they can exert good proliferation and differentiation capabilities after activation after muscle tissue damage. These cells are essential for the repair and regeneration process of skeletal muscle injury.
Fig. 1 Representation of the satellite cell niche. (Bentzinger C F, et al., 2013)
Satellite cells, a type of muscle stem cell, can be identified by various genetic markers. The two commonly expressed markers in most satellite cells are PAX7 and PAX3. However, satellite cells in the head musculature have a different developmental program and do not express Pax3. Another marker used to identify both quiescent (inactive) and activated satellite cells is the neural cell adhesion molecule (N-CAM/CD56/Leu-19), which is found on the cell surface. Additionally, Myocyte nuclear factor (MNF) and c-met proto-oncogene, a receptor for hepatocyte growth factor (HGF), are less commonly used markers.
Quiescent satellite cells are mainly characterized by the presence of CD34 and Myf5 markers. However, identifying activated satellite cells can be challenging as their markers change depending on the degree of activation. As satellite cells become more activated, they progressively lose Pax7 expression and enter the proliferative stage. However, Pax7 is expressed prominently during satellite cell differentiation. Greater activation also leads to increased expression of MyoD, myogenin, and MRF4, which are transcription factors responsible for activating muscle-specific genes. Testing for HGF can also help identify active satellite cells. Furthermore, as satellite cells differentiate, they start expressing muscle-specific filament proteins such as desmin.
Pax7, a paired type homeobox transcription factor, serves as a quantifiable marker for satellite cells in both their quiescent and activated states. It plays a crucial role in the development and survival of satellite cells. Another closely related transcription factor, Pax3, is also expressed in quiescent satellite cells in certain muscles, such as the diaphragm. Both Pax7 and Pax3 are essential for maintaining the proliferation of progenitor cells and preventing premature myogenic differentiation and cell death through apoptosis.
In a state of non-muscle injury, the two types of quiescent satellite cells can be distinguished by the expression of CD34. In the case of high CD34 expression, the cells are more immature and have more stem cell potential. In the case of low CD34 expression, they are ready for differentiation. These distinct subsets of satellite cells play progressive roles in postnatal muscle growth and are regulated by FOXO transcription factors.
Leu-19 is the first antibody used to identify satellite cells by light microscopy in human skeletal muscle. Subsequent studies showed that Leu-19, neural cell adhesion molecule (NCAM), and CD56 antigens share identical immunohistological markers and staining patterns. The NCAM/CD56 antigen is most commonly used to identify satellite cells in human skeletal muscle cryosections. Although the use of NCAM/CD56 is considered a reliable molecular marker for the identification of human skeletal muscle satellite cells, this protein is also expressed in myotubes, myoblasts, and myofibers during development and/or regeneration.
The cell adhesion protein M-cadherin (M-Cad) is one of the alternative markers used to identify human skeletal muscle satellite cells. Some studies have proposed that M-Cad can be used as a recognized marker for satellite cells in animal muscles. Currently, only a few studies have used M-Cad as a molecular marker to successfully detect satellite cells in human skeletal muscle.
Satellite cell markers serve as invaluable tools for identifying and isolating satellite cells from heterogeneous muscle tissue. By targeting specific molecular signatures, researchers can distinguish satellite cells from other cell types and study their behavior under various physiological and pathological conditions. Creative Diagnostics recognizes the significance of satellite cell markers and offers a wide range of high-quality reagents and antibodies for satellite cell research. By leveraging the power of satellite cell markers, researchers can unravel the mysteries of muscle regeneration and pave the way for innovative therapeutic strategies.
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