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Human muscle-derived CLEC14A-positive cells regenerate muscle independent of PAX7

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  • Andreas Marg

    (Muscle Research Unit, Experimental and Clinical Research Center, a joint cooperation of Charité, Universitätsmedizin Berlin and the Max Delbrück Center for Molecular Medicine in the Helmholtz Association)

  • Helena Escobar

    (Muscle Research Unit, Experimental and Clinical Research Center, a joint cooperation of Charité, Universitätsmedizin Berlin and the Max Delbrück Center for Molecular Medicine in the Helmholtz Association
    Max Delbrück Center for Molecular Medicine in the Helmholtz Association)

  • Nikos Karaiskos

    (Max Delbrück Center for Molecular Medicine in the Helmholtz Association
    Berlin Institute of Medical Systems Biology (BIMSB) at the Max Delbrück Center for Molecular Medicine in the Helmholtz Association)

  • Stefanie A. Grunwald

    (Muscle Research Unit, Experimental and Clinical Research Center, a joint cooperation of Charité, Universitätsmedizin Berlin and the Max Delbrück Center for Molecular Medicine in the Helmholtz Association)

  • Eric Metzler

    (Muscle Research Unit, Experimental and Clinical Research Center, a joint cooperation of Charité, Universitätsmedizin Berlin and the Max Delbrück Center for Molecular Medicine in the Helmholtz Association)

  • Janine Kieshauer

    (Muscle Research Unit, Experimental and Clinical Research Center, a joint cooperation of Charité, Universitätsmedizin Berlin and the Max Delbrück Center for Molecular Medicine in the Helmholtz Association
    Max Delbrück Center for Molecular Medicine in the Helmholtz Association)

  • Sascha Sauer

    (Berlin Institute of Medical Systems Biology (BIMSB) at the Max Delbrück Center for Molecular Medicine in the Helmholtz Association
    Berlin Institute of Health)

  • Diana Pasemann

    (Charité Universitätsmedizin Berlin)

  • Edoardo Malfatti

    (INSERM U1179, Université de Versailles Saint-Quentin-en-Yvelines
    Hôpital Universitaire Raymond Poincare)

  • Dominique Mompoint

    (INSERM U1179, Université de Versailles Saint-Quentin-en-Yvelines)

  • Susanna Quijano-Roy

    (INSERM U1179, Université de Versailles Saint-Quentin-en-Yvelines
    Hôpital Universitaire Raymond Poincare)

  • Anastasiya Boltengagen

    (Berlin Institute of Medical Systems Biology (BIMSB) at the Max Delbrück Center for Molecular Medicine in the Helmholtz Association)

  • Joanna Schneider

    (Muscle Research Unit, Experimental and Clinical Research Center, a joint cooperation of Charité, Universitätsmedizin Berlin and the Max Delbrück Center for Molecular Medicine in the Helmholtz Association
    Berlin Institute of Health)

  • Markus Schülke

    (Charité Universitätsmedizin Berlin)

  • Séverine Kunz

    (Max Delbrück Center for Molecular Medicine in the Helmholtz Association
    Electron Microscopy Core Facility, Max Delbrück Center for Molecular Medicine)

  • Robert Carlier

    (INSERM U1179, Université de Versailles Saint-Quentin-en-Yvelines
    Hôpital Universitaire Raymond Poincare)

  • Carmen Birchmeier

    (Max Delbrück Center for Molecular Medicine in the Helmholtz Association)

  • Helge Amthor

    (INSERM U1179, Université de Versailles Saint-Quentin-en-Yvelines
    Hôpital Universitaire Raymond Poincare)

  • Andreas Spuler

    (HELIOS Klinikum Berlin-Buch)

  • Christine Kocks

    (Max Delbrück Center for Molecular Medicine in the Helmholtz Association
    Berlin Institute of Medical Systems Biology (BIMSB) at the Max Delbrück Center for Molecular Medicine in the Helmholtz Association)

  • Nikolaus Rajewsky

    (Max Delbrück Center for Molecular Medicine in the Helmholtz Association
    Berlin Institute of Medical Systems Biology (BIMSB) at the Max Delbrück Center for Molecular Medicine in the Helmholtz Association)

  • Simone Spuler

    (Muscle Research Unit, Experimental and Clinical Research Center, a joint cooperation of Charité, Universitätsmedizin Berlin and the Max Delbrück Center for Molecular Medicine in the Helmholtz Association
    Max Delbrück Center for Molecular Medicine in the Helmholtz Association
    Berlin Institute of Health)

Abstract

Skeletal muscle stem cells, called satellite cells and defined by the transcription factor PAX7, are responsible for postnatal muscle growth, homeostasis and regeneration. Attempts to utilize the regenerative potential of muscle stem cells for therapeutic purposes so far failed. We previously established the existence of human PAX7-positive cell colonies with high regenerative potential. We now identified PAX7-negative human muscle-derived cell colonies also positive for the myogenic markers desmin and MYF5. These include cells from a patient with a homozygous PAX7 c.86-1G > A mutation (PAX7null). Single cell and bulk transcriptome analysis show high intra- and inter-donor heterogeneity and reveal the endothelial cell marker CLEC14A to be highly expressed in PAX7null cells. All PAX7-negative cell populations, including PAX7null, form myofibers after transplantation into mice, and regenerate muscle after reinjury. Transplanted PAX7neg cells repopulate the satellite cell niche where they re-express PAX7, or, strikingly, CLEC14A. In conclusion, transplanted human cells do not depend on PAX7 for muscle regeneration.

Suggested Citation

  • Andreas Marg & Helena Escobar & Nikos Karaiskos & Stefanie A. Grunwald & Eric Metzler & Janine Kieshauer & Sascha Sauer & Diana Pasemann & Edoardo Malfatti & Dominique Mompoint & Susanna Quijano-Roy &, 2019. "Human muscle-derived CLEC14A-positive cells regenerate muscle independent of PAX7," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13650-z
    DOI: 10.1038/s41467-019-13650-z
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    Cited by:

    1. Helena Escobar & Silvia Di Francescantonio & Julia Smirnova & Robin Graf & Stefanie Müthel & Andreas Marg & Alexej Zhogov & Supriya Krishna & Eric Metzler & Mina Petkova & Oliver Daumke & Ralf Kühn & , 2025. "Gene-editing in patient and humanized-mice primary muscle stem cells rescues dysferlin expression in dysferlin-deficient muscular dystrophy," Nature Communications, Nature, vol. 16(1), pages 1-17, December.

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