HOME

TheInfoList



OR:

Myosatellite cells, also known as satellite cells, muscle stem cells or MuSCs, are small
multipotent Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta. According to Latin terms, Pluripotentia means the ability for many thin ...
cells with very little
cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
found in mature
muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
. Satellite cells are precursors to
skeletal muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
cells, able to give rise to satellite cells or differentiated skeletal muscle cells. They have the potential to provide additional
myonuclei Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscle ...
to their parent muscle fiber, or return to a
quiescent Quiescence (/kwiˈɛsəns/) is a state of quietness or inactivity. It may refer to: * Quiescence search, in game tree searching (adversarial search) in artificial intelligence, a quiescent state is one in which a game is considered stable and unl ...
state. More specifically, upon activation, satellite cells can re-enter the cell cycle to proliferate and differentiate into
myoblast Myogenesis is the formation of skeletal muscular tissue, particularly during embryonic development. Muscle fibers generally form through the fusion of precursor myoblasts into multinucleated fibers called ''myotubes''. In the early development o ...
s. Myosatellite cells are located between the
basement membrane The basement membrane is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between Epithelium, epithelial tissues including mesot ...
and the
sarcolemma The sarcolemma (''sarco'' (from ''sarx'') from Greek; flesh, and ''lemma'' from Greek; sheath) also called the myolemma, is the cell membrane surrounding a skeletal muscle fiber or a cardiomyocyte. It consists of a lipid bilayer and a thin oute ...
of muscle fibers, and can lie in grooves either parallel or transversely to the longitudinal axis of the fibre. Their distribution across the fibre can vary significantly. Non-proliferative, quiescent myosatellite cells, which adjoin resting skeletal muscles, can be identified by their distinct location between sarcolemma and basal lamina, a high nuclear-to-cytoplasmic volume ratio, few organelles (e.g. ribosomes, endoplasmic reticulum, mitochondria, golgi complexes), small nuclear size, and a large quantity of nuclear heterochromatin relative to myonuclei. On the other hand, activated satellite cells have an increased number of
caveolae In biology, caveolae ( Latin for "little caves"; singular, caveola), which are a special type of lipid raft, are small (50–100 nanometer) invaginations of the plasma membrane in the cells of many vertebrates. They are the most abundant surface ...
, cytoplasmic organelles, and decreased levels of heterochromatin. Satellite cells are able to differentiate and fuse to augment existing
muscle fibers A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a muscl ...
and to form new fibers. These cells represent the oldest known adult
stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...
niche, and are involved in the normal growth of muscle, as well as regeneration following injury or
disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
. In undamaged muscle, the majority of satellite cells are ''quiescent''; they neither differentiate nor undergo cell division. In response to mechanical strain, satellite cells become ''activated''. Activated satellite cells initially proliferate as skeletal
myoblast Myogenesis is the formation of skeletal muscular tissue, particularly during embryonic development. Muscle fibers generally form through the fusion of precursor myoblasts into multinucleated fibers called ''myotubes''. In the early development o ...
s before undergoing myogenic differentiation.


Structure


Genetic markers

Satellite cells express a number of distinctive
genetic markers A genetic marker is a gene or DNA sequence with a known location on a chromosome that can be used to identify individuals or species. It can be described as a variation (which may arise due to mutation or alteration in the genomic loci) that can be ...
. Current thinking is that most satellite cells express
PAX7 Paired box protein Pax-7 is a protein that in humans is encoded by the ''PAX7'' gene. Function Pax-7 plays a role in neural crest development and gastrulation, and it is an important factor in the expression of neural crest markers such as Slug ...
and
PAX3 The PAX3 (paired box gene 3) gene encodes a member of the paired box or PAX family of transcription factors. The PAX family consists of nine human (PAX1-PAX9) and nine mouse (Pax1-Pax9) members arranged into four subfamilies. Human PAX3 and mouse ...
. Satellite cells in the head musculature have a unique developmental program, and are Pax3-negative. Moreover, both quiescent and activated human satellite cells can be identified by the membrane-bound neural cell adhesion molecule (N-CAM/CD56/Leu-19), a cell-surface glycoprotein. Myocyte nuclear factor (MNF), and c-met proto-oncogene (receptor for hepatocyte growth factor ( HGF)) are less commonly used markers.
CD34 CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species. CD34 derives its name from the cluster of differentiation protocol that identifies cell surface antigens. CD34 was first descri ...
and Myf5 markers specifically define the majority of quiescent satellite cells. Activated satellite cells prove problematic to identify, especially as their markers change with the degree of activation; for example, greater activation results in the progressive loss of Pax7 expression as they enter the proliferative stage. However, Pax7 is expressed prominently after satellite cell differentiation. Greater activation also results in increased expression of myogenic basic helix-loop-helix transcription factors
MyoD MyoD, also known as myoblast determination protein 1, is a protein in animals that plays a major role in regulating muscle differentiation. MyoD, which was discovered in the laboratory of Harold M. Weintraub, belongs to a family of proteins know ...
,
myogenin Myogenin, is a transcriptional activator encoded by the MYOG gene. Myogenin is a muscle-specific basic-helix-loop-helix (bHLH) transcription factor involved in the coordination of skeletal muscle development or myogenesis and repair. Myogenin is ...
, and MRF4 – all responsible for the induction of myocyte-specific genes. HGF testing is also used to identify active satellite cells. Activated satellite cells also begin expressing muscle-specific filament proteins such as
desmin Desmin is a protein that in humans is encoded by the ''DES'' gene. Desmin is a muscle-specific, type III intermediate filament that integrates the sarcolemma, Z disk, and nuclear membrane in sarcomeres and regulates sarcomere architecture. Str ...
as they differentiate. The field of satellite cell biology suffers from the same technical difficulties as other stem cell fields. Studies rely almost exclusively on
Flow cytometry Flow cytometry (FC) is a technique used to detect and measure physical and chemical characteristics of a population of cells or particles. In this process, a sample containing cells or particles is suspended in a fluid and injected into the flo ...
and fluorescence activated cell sorting (FACS) analysis, which gives no information about cell lineage or behaviour. As such, the satellite cell niche is relatively ill-defined and it is likely that it consists of multiple sub-populations.


Function


Muscle repair

When muscle cells undergo injury, quiescent satellite cells are released from beneath the
basement membrane The basement membrane is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between Epithelium, epithelial tissues including mesot ...
. They become activated and re-enter the cell cycle. These dividing cells are known as the "transit amplifying pool" before undergoing myogenic differentiation to form new (post-mitotic) myotubes. There is also evidence suggesting that these cells are capable of fusing with existing myofibers to facilitate growth and repair. The process of muscle regeneration involves considerable remodeling of extracellular matrix and, where extensive damage occurs, is incomplete. Fibroblasts within the muscle deposit scar tissue, which can impair muscle function, and is a significant part of the pathology of
muscular dystrophies Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time. The disorders differ as to which muscles are primarily affe ...
. Satellite cells proliferate following muscle trauma and form new myofibers through a process similar to fetal muscle development. After several cell divisions, the satellite cells begin to fuse with the damaged myotubes and undergo further differentiations and maturation, with peripheral nuclei as in hallmark. One of the first roles described for IGF-1 was its involvement in the proliferation and differentiation of satellite cells. In addition, IGF-1 expression in skeletal muscle extends the capacity to activate satellite cell proliferation (Charkravarthy, et al., 2000), increasing and prolonging the beneficial effects to the aging muscle.


Effects of exercise

Satellite cell activation is measured by the extent of proliferation and differentiation. Typically, satellite cell content is expressed per muscle fiber or as a percentage of total nuclear content, the sum of satellite cell nuclei and myonuclei. While the adaptive response to exercise largely varies on an individual basis on factors such as genetics, age, diet, acclimatization to exercise, and exercise volume, human studies have demonstrated general trends. It is suggested that exercise triggers the release of signaling molecules including inflammatory substances, cytokines and growth factors from surrounding connective tissues and active skeletal muscles. Notably, HGF, a cytokine, is transferred from the extracellular matrix into muscles through the nitric-oxide dependent pathway. It is thought that HGF activates satellite cells, while insulin-like growth factor-I (
IGF-1 Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in molecular structure to insulin which plays an important role in childhood growth, and has anabolic effects in adults. IGF-1 is a protein that in humans is ...
) and
fibroblast growth factor Fibroblast growth factors (FGF) are a family of cell signalling proteins produced by macrophages; they are involved in a wide variety of processes, most notably as crucial elements for normal development in animal cells. Any irregularities in their ...
(FGF) enhance satellite cell proliferation rate following activation. Studies have demonstrated that intense exercise generally increases IGF-1 production, though individual responses vary significantly. More specifically, IGF-1 exists in two isoforms: mechano growth factor (MGF) and IGF-IEa. While the former induces activation and proliferation, the latter causes differentiation of proliferating satellite cells. Human studies have shown that both high resistance training and endurance training have yielded an increased number of satellite cells. These results suggest that a light, endurance training regimen may be useful to counteract the age-correlated satellite cell decrease. In high-resistance training, activation and proliferation of satellite cells are evidenced by increased cyclin D1 mRNA, and
p21 p21Cip1 (alternatively p21Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) that is capable of inhibiting all cyclin/CDK complexes, though is primarily associated ...
mRNA levels. This is consistent with the fact that cyclin D1 and p21 upregulation correlates to division and differentiation of cells. Satellite cell activation has also been demonstrated on an ultrastructural level following exercise.
Aerobic exercise Aerobic exercise (also known as endurance activities, cardio or cardio-respiratory exercise) is physical exercise of low to high intensity that depends primarily on the aerobic energy-generating process. "Aerobic" is defined as "relating to, inv ...
has been shown to significantly increase granular
endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...
, free ribosomes, and mitochondria of the stimulated muscle groups. Additionally, satellite cells have been shown to fuse with muscle fibers, developing new muscle fibers. Other ultrastructural evidence for activated satellite cells include increased concentration of Golgi apparatus and pinocytotic vesicles.


Satellite Cell Activation and Muscle Regeneration

Satellite cells have a crucial role in muscle regeneration due to their ability to proliferate, differentiate, and self-renew. Prior to a severe injury to the muscle, satellite cells are in a dormant state. Slight proliferation can occur in times of light injuries but major injuries require greater numbers of satellite cells to activate. The activation of satellite cells from their dormant state is controlled through signals from the muscle niche. This signaling induces an inflammatory response in the muscle tissue. The behavior of satellite cells is a highly regulated process to accommodate the balance between dormant and active states. In times of injury, satellite cells in myofibers receive signals to proliferate from proteins in the crushed skeletal muscle. Myofibers are fundamental elements in muscle made up of actin and myosin myofibrils. The proteins responsible for signaling the activation of satellite cells are called mitogens. A mitogen is a small protein that induces a cell to enter the cell cycle. When the cells receive signals from the neurons, it causes the myofibers to depolarize and release calcium from the sarcoplasmic reticulum. The release of calcium induces the actin and myosin filaments to move and contract the muscle. Studies found that transplanted satellite cells onto myofibers supported multiple regenerations of new muscle tissue. These findings support the hypothesis that satellite cells are the stem cells in muscles. Dependent on their relative position to daughter cells on myofibers, satellite cells undergo asymmetric and symmetric division. The niche and location determines the behavior of satellite cells in their proliferation and differentiation. In general, mammalian skeletal muscle is relatively stable with little myonuclei turnover. Minor injuries from daily activities can be repaired without inflammation or cell death. Major injuries contribute to myofiber necrosis, inflammation, and cause satellite cells to activate and proliferate. The process of myofiber necrosis to myofiber formation results in muscle regeneration.Yin, Hang; Price, Feodor; Rudnicki, Michael A. (January 2013). "Satellite Cells and the Muscle Stem Cell Niche". ''Physiological Reviews''. 93 (1): 23–67. doi:10.1152/physrev.00043.2011.
ISSN An International Standard Serial Number (ISSN) is an eight-digit serial number used to uniquely identify a serial publication, such as a magazine. The ISSN is especially helpful in distinguishing between serials with the same title. ISSNs ...
0031-9333. PMC 4073943.
PMID PubMed is a free search engine accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine (NLM) at the National Institutes of Health maintain the ...
23303905.
Muscle regeneration occurs in three overlapping stages. The inflammatory response, activation and differentiation of satellite cells, and maturation of the new myofibers are essential for muscle regeneration. This process begins with the death of damaged muscle fibers where dissolution of myofiber sarcolemma leads to an increase in myofiber permeability. The disruption in myofiber integrity is seen in increased plasma levels in muscle proteins. The death of myofibers drives a calcium influx from the sarcoplasmic reticulum to induce tissue degradation. An inflammatory response follows the necrosis of myofibers. During times of muscle growth and regeneration, satellite cells can travel over between myofibers and muscle and over connective tissue barriers. Signals from the damaged environment induce these behavioral changes in satellite cells.


Research

Upon minimal stimulation, satellite cells ''in vitro'' or ''in vivo'' will undergo a myogenic differentiation program. Unfortunately, it seems that transplanted satellite cells have a limited capacity for migration, and are only able to regenerate muscle in the region of the delivery site. As such, systemic treatments or even the treatment of an entire muscle in this way is not possible. However, other cells in the body such as
pericytes Pericytes (previously known as Rouget cells) are multi-functional mural cells of the microcirculation that wrap around the endothelial cells that line the capillaries throughout the body. Pericytes are embedded in the basement membrane of blood c ...
and
hematopoietic stem cells Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the very first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within ...
have all been shown to be able to contribute to muscle repair in a similar manner to the endogenous satellite cell. The advantage of using these cell types for therapy in muscle diseases is that they can be systemically delivered, autonomously migrating to the site of injury. Particularly successful recently has been the delivery of mesoangioblast cells into the
Golden Retriever The Golden Retriever is a Scottish breed of retriever dog of medium size. It is characterised by a gentle and affectionate nature and a striking golden coat. It is commonly kept as a pet and is among the most frequently registered breeds ...
dog model of
Duchenne muscular dystrophy Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy that primarily affects boys. Muscle weakness usually begins around the age of four, and worsens quickly. Muscle loss typically occurs first in the thighs and pelvis fol ...
, which effectively cured the disease. However, the sample size used was relatively small and the study has since been criticized for a lack of appropriate controls for the use of immunosuppressive drugs. Recently, it has been reported that Pax7 expressing cells contribute to dermal wound repair by adopting a fibrotic phenotype through a Wnt/β-catenin mediated process.


Regulation

Little is known of the regulation of satellite cells. Whilst together
PAX3 The PAX3 (paired box gene 3) gene encodes a member of the paired box or PAX family of transcription factors. The PAX family consists of nine human (PAX1-PAX9) and nine mouse (Pax1-Pax9) members arranged into four subfamilies. Human PAX3 and mouse ...
and
PAX7 Paired box protein Pax-7 is a protein that in humans is encoded by the ''PAX7'' gene. Function Pax-7 plays a role in neural crest development and gastrulation, and it is an important factor in the expression of neural crest markers such as Slug ...
currently form the definitive satellite markers, Pax genes are notoriously poor transcriptional activators. The dynamics of activation and quiesence and the induction of the myogenic program through the ''myogenic regulatory factors'', Myf5,
MyoD MyoD, also known as myoblast determination protein 1, is a protein in animals that plays a major role in regulating muscle differentiation. MyoD, which was discovered in the laboratory of Harold M. Weintraub, belongs to a family of proteins know ...
,
myogenin Myogenin, is a transcriptional activator encoded by the MYOG gene. Myogenin is a muscle-specific basic-helix-loop-helix (bHLH) transcription factor involved in the coordination of skeletal muscle development or myogenesis and repair. Myogenin is ...
, and MRF4 remains to be determined. There is some research indicating that satellite cells are negatively regulated by a protein called
myostatin Myostatin (also known as growth differentiation factor 8, abbreviated GDF8) is a protein that in humans is encoded by the ''MSTN'' gene. Myostatin is a myokine that is produced and released by myocytes and acts on muscle cells to inhibit muscle ...
. Increased levels of myostatin up-regulate a
cyclin-dependent kinase Cyclin-dependent kinases (CDKs) are the families of protein kinases first discovered for their role in regulating the cell cycle. They are also involved in regulating transcription, mRNA processing, and the differentiation of nerve cells. They a ...
inhibitor called
p21 p21Cip1 (alternatively p21Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) that is capable of inhibiting all cyclin/CDK complexes, though is primarily associated ...
and thereby inhibit the differentiation of satellite cells.


See also

*
List of human cell types derived from the germ layers This is a list of cells in humans derived from the three embryonic germ layers – ectoderm, mesoderm, and endoderm. Cells derived from ectoderm Surface ectoderm Skin * Trichocyte * Keratinocyte Anterior pituitary * Gonadotrope * Corticotro ...


References


External links


Image at neuro.wustl.edu



NIF Search - Satellite Cell
via the
Neuroscience Information Framework The Neuroscience Information Framework is a repository of global neuroscience web resources, including experimental, clinical, and translational neuroscience databases, knowledge bases, atlases, and genetic/ genomic resources and provides many aut ...
{{Authority control Myoblasts