Muscle stem cells facilitate the long-term regenerative capacity of skeletal muscle. This self-renewing population of satellite cells has only recently been defined through genetic and transplantation experiments. Although muscle stem cells remain in a dormant quiescent state in uninjured muscle, they are poised to activate and produce committed progeny. Unlike committed myogenic progenitor cells, the self-renewal capacity gives muscle stem cells the ability to engraft as satellite cells and capitulate long-term regeneration. Similar to other adult stem cells, understanding the molecular regulation of muscle stem cells has significant implications towards the development of pharmacological or cell-based therapies for muscle disorders. This Cell Science at a Glance article and accompanying poster will review satellite cell characteristics and therapeutic potential, and provide an overview of the muscle stem cell hallmarks: quiescence, self-renewal and commitment. In adult tissue, muscle-derived stem cells are considered a unique cell population that promotes muscle regeneration in response to injury and disease. It is believed that there are at least three subpopulations of muscle stem cells. These include satellite cells, cells in the dorsal aortic wall, and myoblast populations. Undifferentiated satellite cells can be identified by the expression of cell surface markers such as M-cadherin and Caveolin-1.
Muscle Stem Cell Markers Proteins
Satellite cells can be identified by the specific expression of certain proteins. Some markers are intracellular, such as the nuclear membrane proteins lamin A/C (LMNA). Other markers are located at the cell membrane surface, such as syndecans 4, C-X-C chemokine receptor type 4 (CXCR4), neural cell adhesion molecule 1 (NCAM1) and VCAM1.
Lamin A/C also known as LMNA is a protein that in humans is encoded by the LMNA gene. Lamin A/C belongs to the lamin family of proteins. Mutations in the LMNA gene are associated with several diseases, including familial partial lipodystrophy, limb girdle abdomen muscular dystrophy, dilated cardiomyopathy, restricted skin disease, and Hutchinson–Gilford premature aging syndrome.
Syndecan-4 is a transmembrane (type I) heparan sulfate proteoglycan that acts as a receptor in intracellular signaling. Syndecan-4 interacts with the extracellular matrix, anticoagulants and growth factors. It also regulates the cytoskeleton, cell adhesion, and cell migration of actin. Syndecan-4 is upregulated in the endometrium of women with endometriosis, and it is downregulated. Alpha-transferases in endometriotic cells cause a reduction in aggressive growth.
Nerve cell adhesion molecule (NCAM) is a homotypic glycoprotein expressed on the surface of neurons, glial cells and skeletal muscle. NCAM is thought to play a role in cell adhesion, neurite growth, synaptic plasticity, and learning and memory.
CXCR-4 is an alpha chemokine receptor specific for matrix-derived factor 1 (SDF-1, also known as CXCL12), which has potent chemotactic activity on lymphocytes. CXCR4 is up-regulated during the implantation window in the natural and hormone replacement therapy cycle of the endometrium, producing surface polarization of the CXCR4 receptor in the presence of human blastocysts, indicating the adhesion phase of this receptor to human implantation related.
Vascular cell adhesion protein 1 also known as vascular cell adhesion molecule 1 (VCAM-1) or differentiation cluster 106 (CD106) is a protein encoded by the VCAM1 gene in humans. VCAM-1 plays a role in leukocyte endothelial cell signaling and may play a role in the development of atherosclerosis and rheumatoid arthritis.