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Michael A. Rudnicki - One of the best experts on this subject based on the ideXlab platform.

  • The Satellite Cell Niche in Skeletal Muscle
    Biology and Engineering of Stem Cell Niches, 2020
    Co-Authors: Caroline E. Brun, Fabien P. Chevalier, Nicolas A. Dumont, Michael A. Rudnicki
    Abstract:

    Abstract The regenerative capacity of skeletal muscle is due to a population of Satellite Cells known as Satellite stem Cells. Owing to their ability to generate both stem Cells and committed myogenic progenitors, Satellite stem Cells allow self-renewal of the Satellite Cell reservoir and provide myogenic progenitor Cells to repair the muscle tissue. Increasing numbers of studies have highlighted the indispensable role of the niche in the regulation of the stem Cell functions. The niche maintains the muscle stem Cell in a quiescent state but in response to muscle injury, the niche actively generates signals for Satellite Cell activation, proliferation, and differentiation. The cross talk between the muscle stem Cell and its niche is critical and alterations of the niche components result in defective regeneration and muscle pathologies. Here, we describe how the Satellite Cell niche regulates Satellite Cell functions, namely commitment and self-renewal, in resting, injured, and pathologic muscle.

  • intrinsic and extrinsic mechanisms regulating Satellite Cell function
    Development, 2015
    Co-Authors: Nicolas A. Dumont, Michael A. Rudnicki, Yu Xin Wang
    Abstract:

    Muscle stem Cells, termed Satellite Cells, are crucial for skeletal muscle growth and regeneration. In healthy adult muscle, Satellite Cells are quiescent but poised for activation. During muscle regeneration, activated Satellite Cells transiently re-enter the Cell cycle to proliferate and subsequently exit the Cell cycle to differentiate or self-renew. Recent studies have demonstrated that Satellite Cells are heterogeneous and that subpopulations of Satellite stem Cells are able to perform asymmetric divisions to generate myogenic progenitors or symmetric divisions to expand the Satellite Cell pool. Thus, a complex balance between extrinsic cues and intrinsic regulatory mechanisms is needed to tightly control Satellite Cell cycle progression and Cell fate determination. Defects in Satellite Cell regulation or in their niche, as observed in degenerative conditions such as aging, can impair muscle regeneration. Here, we review recent discoveries of the intrinsic and extrinsic factors that regulate Satellite Cell behaviour in regenerating and degenerating muscles.

  • Cellular dynamics in the muscle Satellite Cell niche
    EMBO Reports, 2013
    Co-Authors: Florian C Bentzinger, Nicolas A. Dumont, Michael A. Rudnicki, Yu Xin Wang
    Abstract:

    Satellite Cells, the quintessential skeletal muscle stem Cells, reside in a specialized local environment whose anatomy changes dynamically during tissue regeneration. The plasticity of this niche is attributable to regulation by the stem Cells themselves and to a multitude of functionally diverse Cell types. In particular, immune Cells, fibrogenic Cells, vessel-associated Cells and committed and differentiated Cells of the myogenic lineage have emerged as important constituents of the Satellite Cell niche. Here, we discuss the Cellular dynamics during muscle regeneration and how disease can lead to perturbation of these mechanisms. To define the role of Cellular components in the muscle stem Cell niche is imperative for the development of Cell-based therapies, as well as to better understand the pathobiology of degenerative conditions of the skeletal musculature.

  • fibronectin regulates wnt7a signaling and Satellite Cell expansion
    Cell Stem Cell, 2013
    Co-Authors: Michael A. Rudnicki, Yu Xin Wang, Julia Von Maltzahn, Florian C Bentzinger, Vahab D Soleimani
    Abstract:

    Summary The influence of the extraCellular matrix (ECM) within the stem Cell niche remains poorly understood. We found that Syndecan-4 (Sdc4) and Frizzled-7 (Fzd7) form a coreceptor complex in Satellite Cells and that binding of the ECM glycoprotein Fibronectin (FN) to Sdc4 stimulates the ability of Wnt7a to induce the symmetric expansion of Satellite stem Cells. Newly activated Satellite Cells dynamically remodel their niche via transient high-level expression of FN. Knockdown of FN in prospectively isolated Satellite Cells severely impaired their ability to repopulate the Satellite Cell niche. Conversely, in vivo overexpression of FN with Wnt7a dramatically stimulated the expansion of Satellite stem Cells in regenerating muscle. Therefore, activating Satellite Cells remodel their niche through autologous expression of FN that provides feedback to stimulate Wnt7a signaling through the Fzd7/Sdc4 coreceptor complex. Thus, FN and Wnt7a together regulate the homeostatic levels of Satellite stem Cells and Satellite myogenic Cells during regenerative myogenesis.

  • extrinsic regulation of Satellite Cell specification
    Stem Cell Research & Therapy, 2010
    Co-Authors: Cflorian Bentzinger, Julia Von Maltzahn, Michael A. Rudnicki
    Abstract:

    Cellular commitment during vertebrate embryogenesis is controlled by an interplay of intrinsic regulators and morphogenetic signals. These mechanisms recruit a subset of Cells in the developing organism to become the ancestors of skeletal muscle. Signals that control progression through the myogenic lineage converge on a battery of hierarchically organized transcription factors which modulate the Cells to either remain in a primitive state or allow their commitment and differentiation into skeletal muscle fibers. A small population of Cells will retain a largely unspecified state throughout development. Such stem Cells, in conjunction with more committed myogenic progenitors, form a heterogeneous population that colonizes adult skeletal muscle as Satellite Cells. The Satellite Cell pool is responsible for the remarkable regenerative capacity of skeletal muscle. Similar to their counterparts during embryonic development, Satellite Cells are capable of self-renewal and can give rise to myogenic progeny. Impaired Satellite Cell homeostasis has been associated with numerous muscular disorders. Due to intense research efforts in the past two decades, the complex biology of muscle stem Cells has now revealed some of its secrets and new avenues for the development of therapeutic molecules have emerged. In the present review we focus on the extrinsic mechanisms that control self-renewal, specification and differentiation of Satellite Cells and their significance for the development of biologic drugs.

Laura Collard - One of the best experts on this subject based on the ideXlab platform.

  • srf dependent paracrine signals produced by myofibers control Satellite Cell mediated skeletal muscle hypertrophy
    Cell Metabolism, 2012
    Co-Authors: Aline Guerci, Charlotte Lahoute, Laura Collard, S. Hebrard
    Abstract:

    Summary Adult skeletal muscles adapt their fiber size to workload. We show that serum response factor (Srf) is required for Satellite Cell-mediated hypertrophic muscle growth. Deletion of Srf from myofibers and not Satellite Cells blunts overload-induced hypertrophy, and impairs Satellite Cell proliferation and recruitment to pre-existing fibers. We reveal a gene network in which Srf within myofibers modulates interleukin-6 and cyclooxygenase-2/interleukin-4 expressions and therefore exerts a paracrine control of Satellite Cell functions. In Srf -deleted muscles, in vivo overexpression of interleukin-6 is sufficient to restore Satellite Cell proliferation but not Satellite Cell fusion and overall growth. In contrast cyclooxygenase-2/interleukin-4 overexpression rescue Satellite Cell recruitment and muscle growth without affecting Satellite Cell proliferation, identifying altered fusion as the limiting Cellular event. These findings unravel a role for Srf in the translation of mechanical cues applied to myofibers into paracrine signals, which in turn will modulate Satellite Cell functions and support muscle growth.

  • Srf-dependent paracrine signals produced by myofibers control Satellite Cell-mediated skeletal muscle hypertrophy
    Cell Metabolism, 2012
    Co-Authors: Aline Guerci, Charlotte Lahoute, Laura Collard, Dany Graindorge, Maryline Favier, Nicolas Cagnard, Sabrina Batonnet-pichon, Guillaume Précigout, S. Hebrard, Luis Garcia
    Abstract:

    Adult skeletal muscles adapt their fiber size to workload. We show that serum response factor (Srf) is required for Satellite Cell-mediated hypertrophic muscle growth. Deletion of Srf from myofibers and not Satellite Cells blunts overload-induced hypertrophy, and impairs Satellite Cell proliferation and recruitment to pre-existing fibers. We reveal a gene network in which Srf within myofibers modulates interleukin-6 and cyclooxygenase-2/interleukin-4 expressions and therefore exerts a paracrine control of Satellite Cell functions. In Srf-deleted muscles, in vivo overexpression of interleukin-6 is sufficient to restore Satellite Cell proliferation but not Satellite Cell fusion and overall growth. In contrast cyclooxygenase-2/interleukin-4 overexpression rescue Satellite Cell recruitment and muscle growth without affecting Satellite Cell proliferation, identifying altered fusion as the limiting Cellular event. These findings unravel a role for Srf in the translation of mechanical cues applied to myofibers into paracrine signals, which in turn will modulate Satellite Cell functions and support muscle growth. © 2012 Elsevier Inc.

Thomas A Rando - One of the best experts on this subject based on the ideXlab platform.

  • tissue specific stem Cells lessons from the skeletal muscle Satellite Cell
    Cell Stem Cell, 2012
    Co-Authors: Andrew S Brack, Thomas A Rando
    Abstract:

    In 1961, the Satellite Cell was first identified when electron microscopic examination of skeletal muscle demonstrated a Cell wedged between the plasma membrane of the muscle fiber and the basement membrane. In recent years it has been conclusively demonstrated that the Satellite Cell is the primary Cellular source for muscle regeneration and is equipped with the potential to self renew, thus functioning as a bona fide skeletal muscle stem Cell (MuSC). As we move past the 50 th anniversary of the Satellite Cell, we take this opportunity to discuss the current state of the art and dissect the unknowns in the MuSC field.

  • heterogeneity in the muscle Satellite Cell population
    Seminars in Cell & Developmental Biology, 2010
    Co-Authors: Stefano Biressi, Thomas A Rando
    Abstract:

    Satellite Cells, the adult stem Cells responsible for skeletal muscle regeneration, are defined by their location between the basal lamina and the fiber sarcolemma. Increasing evidence suggests that Satellite Cells represent a heterogeneous population of Cells with distinct embryological origin and multiple levels of biochemical and functional diversity. This review focuses on the rich diversity of the Satellite Cell population based on studies across species. Ultimately, a more complete characterization of the heterogeneity of Satellite Cells will be essential to understand the functional significance in terms of muscle growth, homeostasis, tissue repair, and aging.

  • stem Cells in postnatal myogenesis molecular mechanisms of Satellite Cell quiescence activation and replenishment
    Trends in Cell Biology, 2005
    Co-Authors: Jyotsna Dhawan, Thomas A Rando
    Abstract:

    Satellite Cells are the primary stem Cells in adult skeletal muscle, and are responsible for postnatal muscle growth, hypertrophy and regeneration. In mature muscle, most Satellite Cells are in a quiescent state, but they activate and begin proliferating in response to extrinsic signals. Following activation, a subset of Satellite Cell progeny returns to the quiescent state during the process of self-renewal. Here, we review recent studies of Satellite Cell biology and focus on the key transitions from the quiescent state to the state of proliferative activation and myogenic lineage progression and back to the quiescent state. The molecular mechanisms of these transitions are considered in the context of the biology of the Satellite Cell niche, changes with age, and interactions with established pathways of myogenic commitment and differentiation.

  • the regulation of notch signaling controls Satellite Cell activation and Cell fate determination in postnatal myogenesis
    Developmental Cell, 2002
    Co-Authors: Irina M Conboy, Thomas A Rando
    Abstract:

    Abstract We have studied the role of Notch-1 and its antagonist Numb in the activation of Satellite Cells during postnatal myogenesis. Activation of Notch-1 promoted the proliferation of myogenic precursor Cells expressing the premyoblast marker Pax3. Attenuation of Notch signaling by increases in Numb expression led to the commitment of progenitor Cells to the myoblast Cell fate and the expression of myogenic regulatory factors, desmin, and Pax7. In many intermediate progenitor Cells, Numb was localized asymmetrically in actively dividing Cells, suggesting an asymmetric Cell division and divergent Cell fates of daughter Cells. The results indicate that Satellite Cell activation results in a heterogeneous population of precursor Cells with respect to Notch-1 activity and that the balance between Notch-1 and Numb controls Cellular homeostasis and Cell fate determination.

Bradley B. Olwin - One of the best experts on this subject based on the ideXlab platform.

  • pervasive Satellite Cell contribution to uninjured adult muscle fibers
    Skeletal Muscle, 2015
    Co-Authors: Bradley Pawlikowski, Nicole Dalla Betta, Crystal Pulliam, Gabrielle Kardon, Bradley B. Olwin
    Abstract:

    Background Adult skeletal muscle adapts to functional needs, maintaining consistent numbers of myonuclei and stem Cells. Although resident muscle stem Cells or Satellite Cells are required for muscle growth and repair, in uninjured muscle, these Cells appear quiescent and metabolically inactive. To investigate the Satellite Cell contribution to myofibers in adult uninjured skeletal muscle, we labeled Satellite Cells by inducing a recombination of LSL-tdTomato in Pax7CreER mice and scoring tdTomato+ myofibers as an indicator of Satellite Cell fusion.

  • A role for RNA post-transcriptional regulation in Satellite Cell activation
    Skeletal Muscle, 2012
    Co-Authors: Nicholas H. Farina, D D W Cornelison, Melissa Hausburg, Nicole Dalla Betta, Crystal Pulliam, Deepak Srivastava, Bradley B. Olwin
    Abstract:

    Satellite Cells are resident skeletal muscle stem Cells responsible for muscle maintenance and repair. In resting muscle, Satellite Cells are maintained in a quiescent state. Satellite Cell activation induces the myogenic commitment factor, MyoD, and Cell cycle entry to facilitate transition to a population of proliferating myoblasts that eventually exit the cycle and regenerate muscle tissue. The molecular mechanism involved in the transition of a quiescent Satellite Cell to a transit-amplifying myoblast is poorly understood. Satellite Cells isolated by FACS from uninjured skeletal muscle and 12 h post-muscle injury from wild type and Syndecan-4 null mice were probed using Affymetrix 430v2 gene chips and analyzed by Spotfiretm and Ingenuity Pathway analysis to identify gene expression changes and networks associated with Satellite Cell activation, respectively. Additional analyses of target genes identify miRNAs exhibiting dynamic changes in expression during Satellite Cell activation. The function of the miRNAs was assessed using miRIDIAN hairpin inhibitors. An unbiased gene expression screen identified over 4,000 genes differentially expressed in Satellite Cells in vivo within 12 h following muscle damage and more than 50% of these decrease dramatically. RNA binding proteins and genes involved in post-transcriptional regulation were significantly over-represented whereas splicing factors were preferentially downregulated and mRNA stability genes preferentially upregulated. Furthermore, six computationally identified miRNAs demonstrated novel expression through muscle regeneration and in Satellite Cells. Three of the six miRNAs were found to regulate Satellite Cell fate. The quiescent Satellite Cell is actively maintained in a state poised to activate in response to external signals. Satellite Cell activation appears to be regulated by post-transcriptional gene regulation.

  • coordination of Satellite Cell activation and self renewal by par complex dependent asymmetric activation of p38α β mapk
    Cell Stem Cell, 2012
    Co-Authors: Andrew Troy, Adam B Cadwallader, Yuri V Fedorov, Kristina J Tyner, Kathleen Kelly Tanaka, Bradley B. Olwin
    Abstract:

    Summary In response to muscle injury, Satellite Cells activate the p38α/β MAPK pathway to exit quiescence, then proliferate, repair skeletal muscle, and self-renew, replenishing the quiescent Satellite Cell pool. Although Satellite Cells are capable of asymmetric division, the mechanisms regulating Satellite Cell self-renewal are not understood. We found that Satellite Cells, once activated, enter the Cell cycle and a subset undergoes asymmetric division, renewing the Satellite Cell pool. Asymmetric localization of the Par complex activates p38α/β MAPK in only one daughter Cell, inducing MyoD , which permits Cell cycle entry and generates a proliferating myoblast. The absence of p38α/β MAPK signaling in the other daughter Cell prevents MyoD induction, renewing the quiescent Satellite Cell. Thus, Satellite Cells employ a mechanism to generate distinct daughter Cells, coupling the Par complex and p38α/β MAPK signaling to link the response to muscle injury with Satellite Cell self-renewal.

  • prevention of muscle aging by myofiber associated Satellite Cell transplantation
    Science Translational Medicine, 2010
    Co-Authors: John K Hall, Glen B Banks, Jeffrey S Chamberlain, Bradley B. Olwin
    Abstract:

    Skeletal muscle is dynamic, adapting to environmental needs, continuously maintained, and capable of extensive regeneration. These hallmarks diminish with age, resulting in a loss of muscle mass, reduced regenerative capacity, and decreased functionality. Although the mechanisms responsible for this decline are unclear, complex changes within the local and systemic environment that lead to a reduction in regenerative capacity of skeletal muscle stem Cells, termed Satellite Cells, are believed to be responsible. We demonstrate that engraftment of myofiber-associated Satellite Cells, coupled with an induced muscle injury, markedly alters the environment of young adult host muscle, eliciting a near-lifelong enhancement in muscle mass, stem Cell number, and force generation. The abrogation of age-related atrophy appears to arise from an increased regenerative capacity of the donor stem Cells, which expand to occupy both myonuclei in myofibers and the Satellite Cell niche. Further, these Cells have extensive self-renewal capabilities, as demonstrated by serial transplantation. These near-lifelong, physiological changes suggest an approach for the amelioration of muscle atrophy and diminished function that arise with aging through myofiber-associated Satellite Cell transplantation.

  • the p38α β mapk functions as a molecular switch to activate the quiescent Satellite Cell
    Journal of Cell Biology, 2005
    Co-Authors: Nathan C Jones, D D W Cornelison, Yuri V Fedorov, Kristina J Tyner, Lisa Nibarger, Heather M Stanley, Bradley B. Olwin
    Abstract:

    Somatic stem Cells cycle slowly or remain quiescent until required for tissue repair and maintenance. Upon muscle injury, stem Cells that lie between the muscle fiber and basal lamina (Satellite Cells) are activated, proliferate, and eventually differentiate to repair the damaged muscle. Satellite Cells in healthy muscle are quiescent, do not express MyoD family transcription factors or Cell cycle regulatory genes and are insulated from the surrounding environment. Here, we report that the p38α/β family of mitogen-activated protein kinases (MAPKs) reversibly regulates the quiescent state of the skeletal muscle Satellite Cell. Inhibition of p38α/β MAPKs (a) promotes exit from the Cell cycle, (b) prevents differentiation, and (c) insulates the Cell from most external stimuli allowing the Satellite Cell to maintain a quiescent state. Activation of Satellite Cells and p38α/β MAPKs occurs concomitantly, providing further support that these MAPKs function as a molecular switch for Satellite Cell activation.

D D W Cornelison - One of the best experts on this subject based on the ideXlab platform.

  • A role for RNA post-transcriptional regulation in Satellite Cell activation
    Skeletal Muscle, 2012
    Co-Authors: Nicholas H. Farina, D D W Cornelison, Melissa Hausburg, Nicole Dalla Betta, Crystal Pulliam, Deepak Srivastava, Bradley B. Olwin
    Abstract:

    Satellite Cells are resident skeletal muscle stem Cells responsible for muscle maintenance and repair. In resting muscle, Satellite Cells are maintained in a quiescent state. Satellite Cell activation induces the myogenic commitment factor, MyoD, and Cell cycle entry to facilitate transition to a population of proliferating myoblasts that eventually exit the cycle and regenerate muscle tissue. The molecular mechanism involved in the transition of a quiescent Satellite Cell to a transit-amplifying myoblast is poorly understood. Satellite Cells isolated by FACS from uninjured skeletal muscle and 12 h post-muscle injury from wild type and Syndecan-4 null mice were probed using Affymetrix 430v2 gene chips and analyzed by Spotfiretm and Ingenuity Pathway analysis to identify gene expression changes and networks associated with Satellite Cell activation, respectively. Additional analyses of target genes identify miRNAs exhibiting dynamic changes in expression during Satellite Cell activation. The function of the miRNAs was assessed using miRIDIAN hairpin inhibitors. An unbiased gene expression screen identified over 4,000 genes differentially expressed in Satellite Cells in vivo within 12 h following muscle damage and more than 50% of these decrease dramatically. RNA binding proteins and genes involved in post-transcriptional regulation were significantly over-represented whereas splicing factors were preferentially downregulated and mRNA stability genes preferentially upregulated. Furthermore, six computationally identified miRNAs demonstrated novel expression through muscle regeneration and in Satellite Cells. Three of the six miRNAs were found to regulate Satellite Cell fate. The quiescent Satellite Cell is actively maintained in a state poised to activate in response to external signals. Satellite Cell activation appears to be regulated by post-transcriptional gene regulation.

  • muscle Satellite Cell proliferation and association new insights from myofiber time lapse imaging
    Skeletal Muscle, 2011
    Co-Authors: Ashley L Siegel, Paige K Kuhlmann, D D W Cornelison
    Abstract:

    Background As the resident stem Cells of skeletal muscle, Satellite Cells are activated by extraCellular cues associated with local damage. Once activated, Satellite Cells will re-enter the Cell cycle to proliferate and supply a population of myoblasts, which will repair or replace damaged myofibers by differentiating and fusing either with an existing myofiber or with each other. There is also evidence that the orientation of Cell division with respect to the myofiber may indicate or convey asymmetry in the two daughter Cells. Our recent studies with time-lapse imaging of myofiber-associated Satellite Cells in vitro have yielded new data on the timing and orientation of Satellite Cell divisions, and revealed persistent differences in the behavior of daughter Cells from planar versus vertical divisions.

  • 3d timelapse analysis of muscle Satellite Cell motility
    Stem Cells, 2009
    Co-Authors: Ashley L Siegel, Kevin Atchison, Kevin E Fisher, George E Davis, D D W Cornelison
    Abstract:

    Skeletal muscle repair and regeneration requires the activity of Satellite Cells, a population of myogenic stem Cells scattered throughout the tissue and activated to proliferate and differentiate in response to myotrauma or disease. While it seems likely that Satellite Cells would need to navigate local muscle tissue to reach damaged areas, relatively little data on such motility exist, and most studies have been with immortalized Cell lines. We find that primary Satellite Cells are significantly more motile than myoblast Cell lines, and that adhesion to laminin promotes primary Cell motility more than fourfold over other substrates. Using timelapse videomicroscopy to assess Satellite Cell motility on single living myofibers, we have identified a requirement for the laminin-binding integrin α7β1 in Satellite Cell motility, as well as a role for hepatocyte growth factor in promoting directional persistence. The extensive migratory behavior of Satellite Cells resident on muscle fibers suggests caution when determining, based on fixed specimens, whether adjacent Cells are daughters from the same mother Cell. We also observed more persistent long-term contact between individual Satellite Cells than has been previously supposed, potential Cell-Cell attractive and repulsive interactions, and migration between host myofibers. Based on such activity, we assayed for expression of “pathfinding” cues, and found that Satellite Cells express multiple guidance ligands and receptors. Together, these data suggest that Satellite Cell migration in vivo may be more extensive than currently thought, and could be regulated by combinations of signals, including adhesive haptotaxis, soluble factors, and guidance cues. Stem Cells 2009;27:2527–2538

  • the p38α β mapk functions as a molecular switch to activate the quiescent Satellite Cell
    Journal of Cell Biology, 2005
    Co-Authors: Nathan C Jones, D D W Cornelison, Yuri V Fedorov, Kristina J Tyner, Lisa Nibarger, Heather M Stanley, Bradley B. Olwin
    Abstract:

    Somatic stem Cells cycle slowly or remain quiescent until required for tissue repair and maintenance. Upon muscle injury, stem Cells that lie between the muscle fiber and basal lamina (Satellite Cells) are activated, proliferate, and eventually differentiate to repair the damaged muscle. Satellite Cells in healthy muscle are quiescent, do not express MyoD family transcription factors or Cell cycle regulatory genes and are insulated from the surrounding environment. Here, we report that the p38α/β family of mitogen-activated protein kinases (MAPKs) reversibly regulates the quiescent state of the skeletal muscle Satellite Cell. Inhibition of p38α/β MAPKs (a) promotes exit from the Cell cycle, (b) prevents differentiation, and (c) insulates the Cell from most external stimuli allowing the Satellite Cell to maintain a quiescent state. Activation of Satellite Cells and p38α/β MAPKs occurs concomitantly, providing further support that these MAPKs function as a molecular switch for Satellite Cell activation.

  • syndecan 3 and syndecan 4 specifically mark skeletal muscle Satellite Cells and are implicated in Satellite Cell maintenance and muscle regeneration
    Developmental Biology, 2001
    Co-Authors: D D W Cornelison, Heather M Stanley, Mark S Filla, Alan C Rapraeger, Bradley B. Olwin
    Abstract:

    Myogenesis in the embryo and the adult mammal consists of a highly organized and regulated sequence of Cellular processes to form or repair muscle tissue that include Cell proliferation, migration, and differentiation. Data from Cell culture and in vivo experiments implicate both FGFs and HGF as critical regulators of these processes. Both factors require heparan sulfate glycosaminoglycans for signaling from their respective receptors. Since syndecans, a family of Cell-surface transmembrane heparan sulfate proteoglycans (HSPGs) are implicated in FGF signaling and skeletal muscle differentiation, we examined the expression of syndecans 1‐ 4 in embryonic, fetal, postnatal, and adult muscle tissue, as well as on primary adult muscle fiber cultures. We show that syndecan-1, -3, and -4 are expressed in developing skeletal muscle tissue and that syndecan-3 and -4 expression is highly restricted in adult skeletal muscle to Cells retaining myogenic capacity. These two HSPGs appear to be expressed exclusively and universally on quiescent adult Satellite Cells in adult skeletal muscle tissue, suggesting a role for HSPGs in Satellite Cell maintenance or activation. Once activated, all Satellite Cells maintain expression of syndecan-3 and syndecan-4 for at least 96 h, also implicating these HSPGs in muscle regeneration. Inhibition of HSPG sulfation by treatment of intact myofibers with chlorate results in delayed proliferation and altered MyoD expression, demonstrating that heparan sulfate is required for proper progression of the early Satellite Cell myogenic program. These data suggest that, in addition to providing potentially useful new markers for Satellite Cells, syndecan-3 and syndecan-4 may play important regulatory roles in Satellite Cell maintenance, activation, proliferation, and differentiation during skeletal muscle regeneration. © 2001 Academic Press