13 julio, 2024

Satellite cells: histology and functions

Satellite cells are skeletal muscle cells. They are small, uninucleated cells that are in a quiescent (sleeping) state in adult mammals, which is why it is said that they function as a population of «reserve» cells capable of proliferating under certain conditions.

Skeletal muscle of mammals and many other vertebrates is made up of muscle cells, also called muscle fibers, which are the fully differentiated cells that contain the contractile elements or proteins of this tissue.

These muscle fibers are formed during development thanks to the migration of precursor muscle cells (myoblasts) from the embryonic «somites» to the nascent muscles, where they fuse with each other and form multinucleated muscle cells or myofibers (with more than one nucleus). ).

In adult animals, muscle is formed, or rather regenerated, thanks to the proliferation of satellite cells, which were discovered in 1961 by A. Mauro. These cells are separated from the muscle fibers, since they are found under the basal lamina of each one.

This is a very important type of cell for mammalian muscle tissue, as it probably represents the only cellular source for muscle regeneration in adulthood, whether due to injury, damage, disease, or physical exercise.

Although the term «satellite cell» is also used to distinguish a group of glial cells of the peripheral nervous system, which are located specifically in sensory, sympathetic, and parasympathetic ganglia, it is more commonly used to refer to newly proliferating muscle cells. we mentioned.

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Histology

Satellite cells are formed in the limbs during embryonic development, after the formation of the first muscle fibers (myofibers). These cells are closely associated with the plasma membrane of muscle cells (sarcolemma), as they reside between it and its basal lamina.

They are easily distinguishable due to their location and morphology, although they are very heterogeneous cell populations, that is, with very different cells.

This heterogeneity is based not only on their asymmetric division, but also on the expression of different proteins and transcription factors, on their organization, etc.

satellite cell marker molecules

Muscle satellite cells can be distinguished molecularly from other cells thanks to the concomitant expression of different molecular markers, among which the Pax family transcription factors stand out.

Belonging to this family is the Pax7 transcription factor, which is apparently essential for the maintenance of the «undifferentiated» state of satellite cells, as well as their self-renewal capacity.

These cells also express the Pax3 factor, which is extremely important during the initial steps of muscle formation and is involved in the regulation of the transcription of another marker known as the c-Met receptor tyrosine kinase.

In addition to Pax factors, satellite cells are known to co-express (express at the same time):

– The regulatory factor of myogenesis (muscle formation) known as Myf5

– The transcription factor Barx2, regulator of muscle growth, maintenance and regeneration

– M-cadherin protein, a cell adhesion protein

– The Integrin-7 surface binding receptor

– The differentiation group 34 protein, CD34

– The proteoglycans syndecan-3 and syndecan-4

– The chemokine receptor CXCR4

– The caveolae-forming protein, caveolin-1

– A calcitonin receptor

– The vascular adhesion protein 1, VCAM-1

– The neural cell adhesion molecule 1, NCAM-1

– The nuclear envelope proteins Laminin A, Laminin C and Emerin

Functions of satellite cells

The regenerative characteristics of muscle tissue are mainly due to the action of satellite cells, which function as a «reservoir» of precursor cells, responsible for postnatal growth and muscle regeneration after injury, physical exercise or disease. .

When these cells proliferate, they usually do so asymmetrically, since one part of their progeny fuses with the growing muscle fibers and another is responsible for maintaining the population of regenerative satellite cells.

They are extremely abundant cells during muscle growth, but their number decreases with age.

Muscle regeneration after damage: behavior as «stem» cells

Numerous experimental reports suggest that satellite cells are activated (come out of their normal quiescent state) when skeletal muscle is damaged or after heavy physical exercise.

This “activation” occurs through different signaling pathways and, once activated, these cells proliferate and can do two things: (1) fuse with each other to form “myotubes” that mature to form myofibers or (2) fuse with the segments damaged parts of existing muscle fibers (using them as “scaffolds” or “casts”).

For this reason, these cells are also considered a kind of muscle «stem cells», since they are capable of forming new muscle cells and regenerating the population of satellite cells in the muscle that suffered some unforeseen event.

Balance between quiescence and activation of satellite cells

For many authors, muscle regeneration mediated by satellite cells consists of a series of «steps» that closely resemble the phases of embryonic muscle development.

– Initially the satellite cells have to “come out” of their state of quiescence or dormancy and activate, so that they can begin to divide.

– The division process, as we discussed earlier, is asymmetric, which is necessary for some cells to commit to the formation of new muscle cells and others to maintain the «constant» number of quiescent cells.

– Thus, the myoblasts, that is, the cells produced by satellite cells to regenerate muscle, fuse and form “myotubes”. The myotubes can, in turn, fuse with each other or with a pre-existing fiber to repair it, which will subsequently grow and mature.

The quiescence of the satellite cells must be maintained during the life of the muscle fibers, since they must be activated only when the appropriate signals indicate so.

Some experimental results suggest that, compared to active cells, quiescent satellite cells express 500 more genes, the products of which are likely involved in quiescence.

References

Almeida, CF, Fernandes, SA, Ribeiro Junior, AF, Keith Okamoto, O., & Vainzof, M. (2016). Muscle satellite cells: exploring the basic biology to rule them. Stem cells international, 2016.
Hawke, TJ, & Garry, DJ (2001). Myogenic satellite cells: physiology to molecular biology. Journal of applied physiology, 91(2), 534-551.
Johnson, KE (1991). Histology and cell biology.
Kuehnel, W. (2003). Color Atlas of Cytology, Histology and Microscopic Anatomy. Georg Thieme Verlag.
Morgan, JE, & Partridge, TA (2003). Muscle satellite cells. The international journal of biochemistry & cell biology, 35(8), 1151-1156.
Relaix, F., & Zammit, PS (2012). Satellite cells are essential for skeletal muscle regeneration: the cell on the edge returns center stage. Development, 139(16), 2845-2856.
Wang, YX, & Rudnicki, MA (2012). Satellite cells, the engines of muscle repair. Nature reviews Molecular cell biology, 13(2), 127-133.
Yin, H., Price, F., & Rudnicki, MA (2013). Satellite cells and the muscle stem cell niche. Physiological reviews, 93(1), 23-67.

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