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Isolation, characterization, and molecular regulation of muscle stem cells.

Fukada S, Ma Y, Ohtani T, Watanabe Y, Murakami S, Yamaguchi M - Front Physiol (2013)

Bottom Line: In this review, we summarize the methodology of direct isolation, characterization, and molecular regulation of satellite cells based on our results.The relationship between the regenerative capacity of satellite cells and progression of muscular disorders is also summarized.In the last part, we discuss application of the accumulating scientific information on satellite cells to treatment of patients with muscular disorders.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University Osaka, Japan.

ABSTRACT
Skeletal muscle has great regenerative capacity which is dependent on muscle stem cells, also known as satellite cells. A loss of satellite cells and/or their function impairs skeletal muscle regeneration and leads to a loss of skeletal muscle power; therefore, the molecular mechanisms for maintaining satellite cells in a quiescent and undifferentiated state are of great interest in skeletal muscle biology. Many studies have demonstrated proteins expressed by satellite cells, including Pax7, M-cadherin, Cxcr4, syndecan3/4, and c-met. To further characterize satellite cells, we established a method to directly isolate satellite cells using a monoclonal antibody, SM/C-2.6. Using SM/C-2.6 and microarrays, we measured the genes expressed in quiescent satellite cells and demonstrated that Hesr3 may complement Hesr1 in generating quiescent satellite cells. Although Hesr1- or Hesr3-single knockout mice show a normal skeletal muscle phenotype, including satellite cells, Hesr1/Hesr3-double knockout mice show a gradual decrease in the number of satellite cells and increase in regenerative defects dependent on satellite cell numbers. We also observed that a mouse's genetic background affects the regenerative capacity of its skeletal muscle and have established a line of DBA/2-background mdx mice that has a much more severe phenotype than the frequently used C57BL/10-mdx mice. The phenotype of DBA/2-mdx mice also seems to depend on the function of satellite cells. In this review, we summarize the methodology of direct isolation, characterization, and molecular regulation of satellite cells based on our results. The relationship between the regenerative capacity of satellite cells and progression of muscular disorders is also summarized. In the last part, we discuss application of the accumulating scientific information on satellite cells to treatment of patients with muscular disorders.

No MeSH data available.


Related in: MedlinePlus

Expressions of calcitonin receptor (CTR) and Odz4 proteins during skeletal muscle regeneration. Pax7+MyoD-CTR-Odz4+ cells are frequently observed during myofiber maturation.
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Figure 2: Expressions of calcitonin receptor (CTR) and Odz4 proteins during skeletal muscle regeneration. Pax7+MyoD-CTR-Odz4+ cells are frequently observed during myofiber maturation.

Mentions: Odz is the vertebrate homolog of the Drosophila odd Oz. Odz family proteins belonging to the type II transmembrane protein family (Levine et al., 1994). One member of the Odz family, Odz4, is highly expressed in the central nervous system, developing eyes, and somites (Zhou et al., 2003). In addition, we reported the expression of Odz4 protein in satellite cells (Yamaguchi et al., 2012). The function of Odz4 is little known, but recent reports demonstrated the importance of Odz in oligodendrocyte differentiation and process formation (Suzuki et al., 2012). They also indicated that focal adhesion kinase, a key regulator of cell adhesion, is activated downstream of Odz4. Therefore, in satellite cells, Odz4 might control cell adhesion and/or differentiation. Odz4 and calcitonin receptor are expressed in quiescent satellite cells but not in proliferating myoblasts. Intriguingly, the timings of Odz4 and calcitonin receptor re-expression during skeletal muscle regeneration are different (Yamaguchi et al., 2012). Currently, we do not know the characteristics of Pax7(+)Odz4(+)calcitonin receptor(−) cells, but we have speculated that this type of cell contributes to the maturation of myofibers because the appearance of Pax7(+)Odz4(+)calcitonin receptor(−) cells is observed during maturation of immature myofibers (Figure 2). Like calcitonin receptor genes, the Odz4 intron contains a quiescent satellite cell-specific microRNA, mir-708 (Cheung et al., 2012). The function of mir-708 is also unknown, but the gene expression mechanism of Odz4 might be important for efficient skeletal muscle regeneration.


Isolation, characterization, and molecular regulation of muscle stem cells.

Fukada S, Ma Y, Ohtani T, Watanabe Y, Murakami S, Yamaguchi M - Front Physiol (2013)

Expressions of calcitonin receptor (CTR) and Odz4 proteins during skeletal muscle regeneration. Pax7+MyoD-CTR-Odz4+ cells are frequently observed during myofiber maturation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3824104&req=5

Figure 2: Expressions of calcitonin receptor (CTR) and Odz4 proteins during skeletal muscle regeneration. Pax7+MyoD-CTR-Odz4+ cells are frequently observed during myofiber maturation.
Mentions: Odz is the vertebrate homolog of the Drosophila odd Oz. Odz family proteins belonging to the type II transmembrane protein family (Levine et al., 1994). One member of the Odz family, Odz4, is highly expressed in the central nervous system, developing eyes, and somites (Zhou et al., 2003). In addition, we reported the expression of Odz4 protein in satellite cells (Yamaguchi et al., 2012). The function of Odz4 is little known, but recent reports demonstrated the importance of Odz in oligodendrocyte differentiation and process formation (Suzuki et al., 2012). They also indicated that focal adhesion kinase, a key regulator of cell adhesion, is activated downstream of Odz4. Therefore, in satellite cells, Odz4 might control cell adhesion and/or differentiation. Odz4 and calcitonin receptor are expressed in quiescent satellite cells but not in proliferating myoblasts. Intriguingly, the timings of Odz4 and calcitonin receptor re-expression during skeletal muscle regeneration are different (Yamaguchi et al., 2012). Currently, we do not know the characteristics of Pax7(+)Odz4(+)calcitonin receptor(−) cells, but we have speculated that this type of cell contributes to the maturation of myofibers because the appearance of Pax7(+)Odz4(+)calcitonin receptor(−) cells is observed during maturation of immature myofibers (Figure 2). Like calcitonin receptor genes, the Odz4 intron contains a quiescent satellite cell-specific microRNA, mir-708 (Cheung et al., 2012). The function of mir-708 is also unknown, but the gene expression mechanism of Odz4 might be important for efficient skeletal muscle regeneration.

Bottom Line: In this review, we summarize the methodology of direct isolation, characterization, and molecular regulation of satellite cells based on our results.The relationship between the regenerative capacity of satellite cells and progression of muscular disorders is also summarized.In the last part, we discuss application of the accumulating scientific information on satellite cells to treatment of patients with muscular disorders.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University Osaka, Japan.

ABSTRACT
Skeletal muscle has great regenerative capacity which is dependent on muscle stem cells, also known as satellite cells. A loss of satellite cells and/or their function impairs skeletal muscle regeneration and leads to a loss of skeletal muscle power; therefore, the molecular mechanisms for maintaining satellite cells in a quiescent and undifferentiated state are of great interest in skeletal muscle biology. Many studies have demonstrated proteins expressed by satellite cells, including Pax7, M-cadherin, Cxcr4, syndecan3/4, and c-met. To further characterize satellite cells, we established a method to directly isolate satellite cells using a monoclonal antibody, SM/C-2.6. Using SM/C-2.6 and microarrays, we measured the genes expressed in quiescent satellite cells and demonstrated that Hesr3 may complement Hesr1 in generating quiescent satellite cells. Although Hesr1- or Hesr3-single knockout mice show a normal skeletal muscle phenotype, including satellite cells, Hesr1/Hesr3-double knockout mice show a gradual decrease in the number of satellite cells and increase in regenerative defects dependent on satellite cell numbers. We also observed that a mouse's genetic background affects the regenerative capacity of its skeletal muscle and have established a line of DBA/2-background mdx mice that has a much more severe phenotype than the frequently used C57BL/10-mdx mice. The phenotype of DBA/2-mdx mice also seems to depend on the function of satellite cells. In this review, we summarize the methodology of direct isolation, characterization, and molecular regulation of satellite cells based on our results. The relationship between the regenerative capacity of satellite cells and progression of muscular disorders is also summarized. In the last part, we discuss application of the accumulating scientific information on satellite cells to treatment of patients with muscular disorders.

No MeSH data available.


Related in: MedlinePlus