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      Identification and Characterization of the Dermal Panniculus Carnosus Muscle Stem Cells

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          Summary

          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.

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          Highlights

          • 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

          Abstract

          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 references51

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          A Pax3/Pax7-dependent population of skeletal muscle progenitor cells.

          During vertebrate development, successive phases of embryonic and fetal myogenesis lead to the formation and growth of skeletal muscles. Although the origin and molecular regulation of the earliest embryonic muscle cells is well understood, less is known about later stages of myogenesis. We have identified a new cell population that expresses the transcription factors Pax3 and Pax7 (paired box proteins 3 and 7) but no skeletal-muscle-specific markers. These cells are maintained as a proliferating population in embryonic and fetal muscles of the trunk and limbs throughout development. Using a stable green fluorescent protein (GFP) reporter targeted to Pax3, we demonstrate that they constitute resident muscle progenitor cells that subsequently become myogenic and form skeletal muscle. Late in fetal development, these cells adopt a satellite cell position characteristic of progenitor cells in postnatal muscle. In the absence of both Pax3 and Pax7, further muscle development is arrested and only the early embryonic muscle of the myotome forms. Cells failing to express Pax3 or Pax7 die or assume a non-myogenic fate. We conclude that this resident Pax3/Pax7-dependent progenitor cell population constitutes a source of myogenic cells of prime importance for skeletal muscle formation, a finding also of potential value in the context of cell therapy for muscle disease.
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            Gene regulatory networks and transcriptional mechanisms that control myogenesis.

            We discuss the upstream regulators of myogenesis that lead to the activation of myogenic determination genes and subsequent differentiation, focusing on the mouse model. Key upstream genes, such as Pax3 and Pax7, Six1 and Six4, or Pitx2, participate in gene regulatory networks at different sites of skeletal muscle formation. MicroRNAs also intervene, with emerging evidence for the role of other noncoding RNAs. Myogenic determination and subsequent differentiation depend on members of the MyoD family. We discuss new insights into mechanisms underlying the transcriptional activity of these factors. Copyright © 2014 Elsevier Inc. All rights reserved.
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              Muscle regeneration by bone marrow-derived myogenic progenitors.

              Growth and repair of skeletal muscle are normally mediated by the satellite cells that surround muscle fibers. In regenerating muscle, however, the number of myogenic precursors exceeds that of resident satellite cells, implying migration or recruitment of undifferentiated progenitors from other sources. Transplantation of genetically marked bone marrow into immunodeficient mice revealed that marrow-derived cells migrate into areas of induced muscle degeneration, undergo myogenic differentiation, and participate in the regeneration of the damaged fibers. Genetically modified, marrow-derived myogenic progenitors could potentially be used to target therapeutic genes to muscle tissue, providing an alternative strategy for treatment of muscular dystrophies.
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                Author and article information

                Contributors
                Journal
                Stem Cell Reports
                Stem Cell Reports
                Stem Cell Reports
                Elsevier
                2213-6711
                01 September 2016
                13 September 2016
                01 September 2016
                : 7
                : 3
                : 411-424
                Affiliations
                [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@ 123456nanogune.eu
                [∗∗ ]Corresponding author ander.izeta@ 123456biodonostia.org
                Article
                S2213-6711(16)30152-7
                10.1016/j.stemcr.2016.08.002
                5032673
                27594590
                1085023a-55ea-438c-9401-c83366c8c0bb
                © 2016 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 7 April 2015
                : 1 August 2016
                : 1 August 2016
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