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

Andreas Marg, Helena Escobar, Nikos Karaiskos, Stefanie A. Grunwald, Eric Metzler, Janine Kieshauer, Sascha Sauer, Diana Pasemann, Edoardo Malfatti, Dominique Mompoint, Susanna Quijano-Roy, Anastasiya Boltengagen, Joanna Schneider, Markus Schülke, Séverine Kunz, Robert Carlier, Carmen Birchmeier, Helge Amthor, Andreas Spuler, Christine Kocks, Nikolaus Rajewsky and Simone Spuler ()
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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
Nikos Karaiskos: 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
Sascha Sauer: Berlin Institute of Medical Systems Biology (BIMSB) at the Max Delbrück Center for Molecular Medicine in the Helmholtz Association
Diana Pasemann: Charité Universitätsmedizin Berlin
Edoardo Malfatti: INSERM U1179, Université de Versailles Saint-Quentin-en-Yvelines
Dominique Mompoint: INSERM U1179, Université de Versailles Saint-Quentin-en-Yvelines
Susanna Quijano-Roy: INSERM U1179, Université de Versailles Saint-Quentin-en-Yvelines
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
Markus Schülke: Charité Universitätsmedizin Berlin
Séverine Kunz: Max Delbrück Center for Molecular Medicine in the Helmholtz Association
Robert Carlier: INSERM U1179, Université de Versailles Saint-Quentin-en-Yvelines
Carmen Birchmeier: Max Delbrück Center for Molecular Medicine in the Helmholtz Association
Helge Amthor: INSERM U1179, Université de Versailles Saint-Quentin-en-Yvelines
Andreas Spuler: HELIOS Klinikum Berlin-Buch
Christine Kocks: Max Delbrück Center for Molecular Medicine in the Helmholtz Association
Nikolaus Rajewsky: 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

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-13650-z

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