Calcitonin receptor and Odz4 are differently expressed in Pax7-positive cells during skeletal muscle regeneration (original) (raw)
Related papers
Molecular Signature of Quiescent Satellite Cells in Adult Skeletal Muscle
Stem Cells, 2007
Skeletal muscle satellite cells play key roles in postnatal muscle growth and regeneration. To study molecular regulation of satellite cells, we directly prepared satellite cells from 8-to 12-week-old C57BL/6 mice and performed genome-wide gene expression analysis. Compared with activated/cycling satellite cells, 507 genes were highly upregulated in quiescent satellite cells. These included negative regulators of cell cycle and myogenic inhibitors. Gene set enrichment analysis revealed that quiescent satellite cells preferentially express the genes involved in cell-cell adhesion, regulation of cell growth, formation of extracellular matrix, copper and iron homeostasis, and lipid transportation. Furthermore, reverse transcriptionpolymerase chain reaction on differentially expressed genes confirmed that calcitonin receptor (CTR) was exclusively expressed in dormant satellite cells but not in activated satellite cells. In addition, CTR mRNA is hardly detected in nonmyogenic cells. Therefore, we next examined the expression of CTR in vivo. CTR was specifically expressed on quiescent satellite cells, but the expression was not found on activated/proliferating satellite cells during muscle regeneration. CTR-positive cells reappeared at the rim of regenerating myofibers in later stages of muscle regeneration. Calcitonin stimulation delayed the activation of quiescent satellite cells. Our data provide roles of CTR in quiescent satellite cells and a solid scaffold to further dissect molecular regulation of satellite cells.
Skeletal muscle progenitor cells in development and regeneration
In mammals, the repair of skeletal muscle damage in the adult shares many features with embryonic muscle formation. The aim of this review is to outline the cellular and molecular mechanisms that govern muscle development and regeneration. Skeletal muscle tissue is comprised of multinucleated myofibres that arise from the fusion of mononucleated myoblasts during embryonic development. In muscle precursor cells, elaborate mechanisms co-ordinate regulation of the cell cycle with the onset of tissue-specific gene expression and may protect these progenitors from precocious differentiation. Differentiated myofibres are incapable of resuming active proliferation, but damaged adult muscle can regenerate. This regenerative capacity resides in a population of undifferentiated myogenic precursor cells known as satellite cells (SC) that are associated with the myofibres. SC contribute to postnatal muscle fibre growth as well as regeneration and are believed to function as the stem cells of ad...
Muscle satellite cells adopt divergent fates: a mechanism for self-renewal?
Journal of Cell Biology, 2004
rowth, repair, and regeneration of adult skeletal muscle depends on the persistence of satellite cells: muscle stem cells resident beneath the basal lamina that surrounds each myofiber. However, how the satellite cell compartment is maintained is unclear. Here, we use cultured myofibers to model muscle regeneration and show that satellite cells adopt divergent fates. Quiescent satellite cells are synchronously activated to coexpress the transcription factors Pax7 and MyoD. Most then proliferate, down-regulate Pax7, and differentiate. In contrast, other G proliferating cells maintain Pax7 but lose MyoD and withdraw from immediate differentiation. These cells are typically located in clusters, together with Pax7 Ϫ ve progeny destined for differentiation. Some of the Pax7 ϩ ve/MyoD Ϫ ve cells then leave the cell cycle, thus regaining the quiescent satellite cell phenotype. Significantly, noncycling cells contained within a cluster can be stimulated to proliferate again. These observations suggest that satellite cells either differentiate or switch from terminal myogenesis to maintain the satellite cell pool.
Adult satellite cells and embryonic muscle progenitors have distinct genetic requirements
Nature, 2009
Myogenic potential, survival and expansion of mammalian muscle progenitors depend on the myogenic determinants Pax3 and Pax7 embryonically 1 , and Pax7 alone perinatally . Several in vitro studies support Pax7's critical role in these functions of adult muscle stem cells 5-8 , i.e. satellite cells, but a formal demonstration has been lacking in vivo. Applying inducible Cre/loxP lineage tracing 9 and conditional gene inactivation to the tibialis anterior muscle regeneration paradigm, we show unexpectedly that when Pax7 is inactivated in adult mice, mutant satellite cells are not compromised in muscle regeneration, can proliferate and reoccupy the sublaminal satellite niche, and support further regenerative processes. Surprisingly, dual adult inactivation of Pax3 and Pax7 also results in normal muscle regeneration. Multiple time points of gene inactivation reveal Pax7 is only required up to the juvenile period when progenitor cells transition into quiescence. We further demonstrate a cell intrinsic difference between neonatal progenitor and adult satellite cells in their Pax7-dependency. Our finding of an age-dependent change in the genetic requirement for muscle stem cells cautions against inferring adult stem cell biology from embryonic studies, and has direct implications for the use of stem cells from hosts of different ages in transplantation-based therapy.
Six family genes control the proliferation and differentiation of muscle satellite cells
Experimental Cell Research, 2010
Muscle satellite cells are essential for muscle growth and regeneration and their morphology, behavior and gene expression have been extensively studied. However, the mechanisms involved in their proliferation and differentiation remain elusive. Six1 and Six4 proteins were expressed in the nuclei of myofibers of adult mice and the numbers of myoblasts positive for Six1 and Six4 increased during regeneration of skeletal muscles. Six1 and Six4 were expressed in quiescent, activated and differentiated muscle satellite cells isolated from adult skeletal muscle.
Muscle Satellite Cell Protein Teneurin-4 Regulates Differentiation during Muscle Regeneration
Stem cells (Dayton, Ohio), 2015
Satellite cells are maintained in an undifferentiated quiescent state, but during muscle regeneration they acquire an activated stage, and initiate to proliferate and differentiate as myoblasts. The transmembrane protein teneurin-4 (Ten-4) is specifically expressed in the quiescent satellite cells; however, its cellular and molecular function remains unknown. We therefore aimed to elucidate the function of Ten-4 in muscle satellite cells. In the tibialis anterior (TA) muscle of Ten-4 deficient mice, the number and the size of myofibers, as well as the population of satellite cells, were reduced with/without induction of muscle regeneration. Further, we found an accelerated activation of satellite cells in the regenerated Ten-4 deficient TA muscle. The cell culture analysis using primary satellite cells showed that Ten-4 suppressed the progression of myogenic differentiation. Together, our findings revealed that Ten-4 functions as a crucial player in maintaining the quiescence of mus...
PLoS ONE, 2009
Satellite cells are the resident stem cells of adult skeletal muscle. To date though, there is a paucity of native markers that can be used to easily identify quiescent satellite cells, with Pax7 probably being the best that is currently available. Here we have further characterized a number of recently described satellite cell markers, and also describe novel ones. Caveolin-1, integrin a7 and the calcitonin receptor proved reliable markers for quiescent satellite cells, being expressed by all satellite cells identified with Pax7. These three markers remained expressed as satellite cells were activated and underwent proliferation. The nuclear envelope proteins lamin A/C and emerin, mutations in which underlie Emery-Dreifuss muscular dystrophy, were also expressed in both quiescent and proliferating satellite cells. Conversely, Jagged-1, a Notch ligand, was not expressed in quiescent satellite cells but was induced upon activation. These findings further contribute to defining the molecular signature of muscle satellite cells. Citation: Gnocchi VF, White RB, Ono Y, Ellis JA, Zammit PS (2009) Further Characterisation of the Molecular Signature of Quiescent and Activated Mouse Muscle Satellite Cells. PLoS ONE 4(4): e5205.
Defining the transcriptional signature of skeletal muscle stem cells1,2
Journal of Animal Science, 2007
Satellite cells, the main source of myoblasts in postnatal muscle, are located beneath the myofiber basal lamina. The myogenic potential of satellite cells was initially documented based on their capacity to produce progeny that fused into myotubes. More recently, molecular markers of resident satellite cells were identified, further contributing to defining these cells as myogenic stem cells that produce differentiating progeny and self-renew. Herein, we discuss aspects of the satellite cell transcriptional milieu that have been intensively investigated in our research. We elaborate on the expression patterns of the paired box (Pax) transcription factors Pax3 and Pax7, and on the myogenic regulatory factors myogenic factor 5 (Myf5), myogenic determination factor 1 (MyoD), and myogenin. We also introduce original data on MyoD upregulation in newly activated satellite cells, which precedes the first round of cell proliferation. Such MyoD upregulation occurred even when parent myofibers with their associated satellite cells were exposed to pharmacological inhibitors of hepatocyte growth factor and fibroblast growth factor receptors, which are typically involved in promoting satellite cell proliferation. These observations support the hypothesis that most satellite cells in adult muscle are committed to rapidly entering myogenesis. We also detected expression of serum response factor in resident satellite cells prior to MyoD expression, which may facilitate the rapid upregulation of MyoD. Aspects of satellite cell self-renewal based on the reemergence of cells expressing Pax7, but not MyoD, in myogenic cultures are discussed further herein. We conclude by describing our recent studies using transgenic mice in which satellite cells are traced and isolated based on their expression of green fluorescence protein driven by regulatory elements of the nestin promoter (nestin-green fluorescence protein). This feature provides us with a novel means of studying satellite cell transcriptional signatures, heterogeneity among muscle groups, and the role of the myogenic niche in directing satellite cell self-renewal.