General Immunology and Microbiology; General Biochemistry, Genetics and Molecular Biology; General Medicine; General Neuroscience
Abstract :
[en] In vitro culture systems that structurally model human myogenesis and promote PAX7+ myogenic progenitor maturation have not been established. Here we report that human skeletal muscle organoids can be differentiated from induced pluripotent stem cell lines to contain paraxial mesoderm and neuromesodermal progenitors and develop into organized structures reassembling neural plate border and dermomyotome. Culture conditions instigate neural lineage arrest and promote fetal hypaxial myogenesis toward limb axial anatomical identity, with generation of sustainable uncommitted PAX7 myogenic progenitors and fibroadipogenic (PDGFRa+) progenitor populations equivalent to those from the second trimester of human gestation. Single-cell comparison to human fetal and adult myogenic progenitor /satellite cells reveals distinct molecular signatures for non-dividing myogenic progenitors in activated (CD44High/CD98+/MYOD1+) and dormant (PAX7High/FBN1High/SPRY1High) states. Our approach provides a robust 3D in vitro developmental system for investigating muscle tissue morphogenesis and homeostasis.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Mavrommatis, Lampros; Ruhr University Bochum, Medical Faculty, Institute of Anatomy, Department of Anatomy and Molecular Embryology ; Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology ; Department of Neurology with Heimer Institute for Muscle Research, University Hospital Bergmannsheil
Jeong, Hyun-Woo ; Max Planck Institute for Molecular Biomedicine, Sequencing Core Facility
Kindler, Urs ; Ruhr University Bochum, Medical Faculty, Institute of Anatomy, Department of Anatomy and Molecular Embryology
Gomez-Giro, Gemma; Luxembourg Centre for Systems Biomedicine, LCSB, Developmental and Cellular Biology, University of Luxembourg
Kienitz, Marie-Cecile; Ruhr University Bochum, Medical Faculty, Department of Cellular Physiology
Stehling, Martin; Max Planck Institute for Molecular Biomedicine, Flow Cytometry Unit
Psathaki, Olympia E; Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology ; Center for Cellular Nanoanalytics Osnabrück, CellNanOs, University of Osnabrück
Zeuschner, Dagmar ; Max Planck Institute for Molecular Biomedicine, Electron Microscopy Unit
Bixel, M Gabriele; Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis
Han, Dong; Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology
Morosan-Puopolo, Gabriela; Ruhr University Bochum, Medical Faculty, Institute of Anatomy, Department of Anatomy and Molecular Embryology
Gerovska, Daniela; Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute
Yang, Ji Hun; School of Mechanical Engineering, Korea University ; R&D Research Center, Next & Bio Inc
Kim, Jeong Beom ; School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST)
Arauzo-Bravo, Marcos J ; Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute
SCHWAMBORN, Jens Christian ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Developmental and Cellular Biology
Hahn, Stephan A ; Ruhr University Bochum, Medical Faculty, Department of Molecular GI Oncology
Adams, Ralf H ; Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis ; Westphalian Wilhelms University Münster, Medical Faculty
Schöler, Hans R; Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology
Vorgerd, Matthias; Department of Neurology with Heimer Institute for Muscle Research, University Hospital Bergmannsheil
Brand-Saberi, Beate; Ruhr University Bochum, Medical Faculty, Institute of Anatomy, Department of Anatomy and Molecular Embryology
Zaehres, Holm ; Ruhr University Bochum, Medical Faculty, Institute of Anatomy, Department of Anatomy and Molecular Embryology ; Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology
