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Identification and Characterization of the Dermal Panniculus Carnosus Muscle Stem Cells

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      The dermal Panniculus carnosus (PC) muscle is important for wound contraction in lower mammals and represents an interesting model of muscle regeneration due to its high cell turnover. The resident satellite cells (the bona fide muscle stem cells) remain poorly characterized. Here we analyzed PC satellite cells with regard to developmental origin and purported function. Lineage tracing shows that they originate in Myf5 + , Pax3/ Pax7 + cell populations. Skin and muscle wounding increased PC myofiber turnover, with the satellite cell progeny being involved in muscle regeneration but with no detectable contribution to the wound-bed myofibroblasts. Since hematopoietic stem cells fuse to PC myofibers in the absence of injury, we also studied the contribution of bone marrow-derived cells to the PC satellite cell compartment, demonstrating that cells of donor origin are capable of repopulating the PC muscle stem cell niche after irradiation and bone marrow transplantation but may not fully acquire the relevant myogenic commitment.

      Graphical Abstract


      • PC satellite cells originate from Myf5 + , Pax3/Pax7 + cell lineages
      • Skin and muscle wounding increase PC myofiber turnover
      • Donor bone marrow cells repopulate the PC satellite niche after BMT
      • Dermis-derived myogenesis originates from the PC satellite cell population


      In this article, Izeta, García-Parra, and colleagues show that the panniculus carnosus (PC) muscle satellite cells originate from a somitic Pax3/7-positive and Myf5-positive lineage, like limb and body wall skeletal muscles. Through lineage tracing, cell sorting, and ablation experiments they unambiguously demonstrate that the only dermal cells with a myogenic potential are the PC satellite cells and their progeny.

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      Most cited references 65

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      Gene Expression Omnibus: NCBI gene expression and hybridization array data repository.

      The Gene Expression Omnibus (GEO) project was initiated in response to the growing demand for a public repository for high-throughput gene expression data. GEO provides a flexible and open design that facilitates submission, storage and retrieval of heterogeneous data sets from high-throughput gene expression and genomic hybridization experiments. GEO is not intended to replace in house gene expression databases that benefit from coherent data sets, and which are constructed to facilitate a particular analytic method, but rather complement these by acting as a tertiary, central data distribution hub. The three central data entities of GEO are platforms, samples and series, and were designed with gene expression and genomic hybridization experiments in mind. A platform is, essentially, a list of probes that define what set of molecules may be detected. A sample describes the set of molecules that are being probed and references a single platform used to generate its molecular abundance data. A series organizes samples into the meaningful data sets which make up an experiment. The GEO repository is publicly accessible through the World Wide Web at
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          An absolute requirement for Pax7-positive satellite cells in acute injury-induced skeletal muscle regeneration.

          Skeletal muscle tissue provides mechanical force for locomotion of all vertebrate animals. It is prone to damage from acute physical trauma and physiological stress. To cope with this, it possesses a tremendous capacity for rapid and effective repair that is widely held to be accomplished by the satellite cells lying between the muscle fiber plasmalemma and the basement membrane. Cell transplantation and lineage-tracing studies have demonstrated that Pax7-expressing (Pax7(+)) satellite cells can repair damaged muscle tissue repeatedly after several bouts of acute injury. These findings provided evidence that Pax7(+) cells are muscle stem cells. However, stem cells from a variety of other origins are also reported to contribute to myofibers upon engraftment into muscles, questioning whether satellite cells are the only stem cell source for muscle regeneration. Here, we have engineered genetic ablation of Pax7(+) cells to test whether there is any significant contribution to muscle regeneration after acute injury from cells other than this source. We find that such elimination of Pax7(+) cells completely blocks regenerative myogenesis either following injury to the tibialis anterior (TA) muscle or after transplantation of extensor digitorum longus (EDL) muscles into nude mice. As Pax7 is specifically expressed in satellite cells, we conclude that they are essential for acute injury-induced muscle regeneration. It remains to be established whether there is any significant role for stem cells of other origins. The implications of our results for muscle stem cell-based therapy are discussed.

            Author and article information

            [1 ]Tissue Engineering Laboratory, Bioengineering Area, Instituto Biodonostia, San Sebastián 20014, Spain
            [2 ]Neuroscience Area, Instituto Biodonostia, San Sebastián 20014, Spain
            [3 ]CIBERNED, Instituto de Salud Carlos III, Madrid 28029, Spain
            [4 ]INSERM U955-E10, Université Paris Est, Faculté de Médicine, IMRB U955-E10, Creteil 94000, France
            [5 ]Molecular Embryology Team, Centro Andaluz de Biología del Desarrollo, Sevilla 41013, Spain
            [6 ]Laboratorio de Neurobiología Comparada, Instituto Cavanilles, Universidad de Valencia, Valencia 46980, Spain
            [7 ]Faculty of Medicine and Nursing, UPV-EHU, San Sebastián 20014, Spain
            [8 ]Animal Facility and Experimental Surgery, Instituto Biodonostia, San Sebastián 20014, Spain
            [9 ]Computational Biology and Systems Biomedicine, Instituto Biodonostia, San Sebastián 20014, Spain
            [10 ]IKERBASQUE, Basque Foundation for Science, Bilbao 48013, Spain
            [11 ]INSA, UPS, INP, LISBP, Université de Toulouse, 31077 Toulouse, France
            [12 ]INRA, UMR792, Ingénierie des Systèmes Biologiques et des Procédés, 31400 Toulouse, France
            [13 ]CNRS, UMR5504, 31400 Toulouse, France
            [14 ]Immunology and Oncology Department, Spanish National Center for Biotechnology (CNB-CSIC), Madrid 28049, Spain
            [15 ]Cellular Oncology Group, Oncology Area, Instituto Biodonostia, San Sebastián 20014, Spain
            [16 ]Faculty of Medicine and Nursing, Department of Neurosciences, UPV-EHU, San Sebastián 20014, Spain
            [17 ]Department of Neurology, Hospital Universitario Donostia, San Sebastián 20014, Spain
            [18 ]Department of Biomedical Engineering, School of Engineering, Tecnun-University of Navarra, San Sebastián 20009, Spain
            Author notes
            []Corresponding author pgarcia@
            [∗∗ ]Corresponding author ander.izeta@
            Stem Cell Reports
            Stem Cell Reports
            Stem Cell Reports
            01 September 2016
            13 September 2016
            01 September 2016
            : 7
            : 3
            : 411-424
            © 2016 The Author(s)

            This is an open access article under the CC BY-NC-ND license (



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