eLife (Nov 2023)
Human skeletal muscle organoids model fetal myogenesis and sustain uncommitted PAX7 myogenic progenitors
- Lampros Mavrommatis,
- Hyun-Woo Jeong,
- Urs Kindler,
- Gemma Gomez-Giro,
- Marie-Cecile Kienitz,
- Martin Stehling,
- Olympia E Psathaki,
- Dagmar Zeuschner,
- M Gabriele Bixel,
- Dong Han,
- Gabriela Morosan-Puopolo,
- Daniela Gerovska,
- Ji Hun Yang,
- Jeong Beom Kim,
- Marcos J Arauzo-Bravo,
- Jens C Schwamborn,
- Stephan A Hahn,
- Ralf H Adams,
- Hans R Schöler,
- Matthias Vorgerd,
- Beate Brand-Saberi,
- Holm Zaehres
Affiliations
- Lampros Mavrommatis
- Ruhr University Bochum, Medical Faculty, Institute of Anatomy, Department of Anatomy and Molecular Embryology, Bochum, Germany; Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology, Münster, Germany; Department of Neurology with Heimer Institute for Muscle Research, University Hospital Bergmannsheil, Bochum, Germany
- Hyun-Woo Jeong
- ORCiD
- Max Planck Institute for Molecular Biomedicine, Sequencing Core Facility, Münster, Germany
- Urs Kindler
- ORCiD
- Ruhr University Bochum, Medical Faculty, Institute of Anatomy, Department of Anatomy and Molecular Embryology, Bochum, Germany
- Gemma Gomez-Giro
- Luxembourg Centre for Systems Biomedicine, LCSB, Developmental and Cellular Biology, University of Luxembourg, Belvaux, Luxembourg
- Marie-Cecile Kienitz
- Ruhr University Bochum, Medical Faculty, Department of Cellular Physiology, Bochum, Germany
- Martin Stehling
- Max Planck Institute for Molecular Biomedicine, Flow Cytometry Unit, Münster, Germany
- Olympia E Psathaki
- Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology, Münster, Germany; Center for Cellular Nanoanalytics Osnabrück, CellNanOs, University of Osnabrück, Osnabrück, Germany
- Dagmar Zeuschner
- ORCiD
- Max Planck Institute for Molecular Biomedicine, Electron Microscopy Unit, Münster, Germany
- M Gabriele Bixel
- Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, Münster, Germany
- Dong Han
- Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology, Münster, Germany
- Gabriela Morosan-Puopolo
- Ruhr University Bochum, Medical Faculty, Institute of Anatomy, Department of Anatomy and Molecular Embryology, Bochum, Germany
- Daniela Gerovska
- Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastián, Spain
- Ji Hun Yang
- School of Mechanical Engineering, Korea University, Seoul, Republic of Korea; R&D Research Center, Next & Bio Inc, Seoul, Republic of Korea
- Jeong Beom Kim
- ORCiD
- School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea
- Marcos J Arauzo-Bravo
- ORCiD
- Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastián, Spain
- Jens C Schwamborn
- ORCiD
- Luxembourg Centre for Systems Biomedicine, LCSB, Developmental and Cellular Biology, University of Luxembourg, Belvaux, Luxembourg
- Stephan A Hahn
- ORCiD
- Ruhr University Bochum, Medical Faculty, Department of Molecular GI Oncology, Bochum, Germany
- Ralf H Adams
- ORCiD
- Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, Münster, Germany; Westphalian Wilhelms University Münster, Medical Faculty, Münster, Germany
- Hans R Schöler
- Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology, Münster, Germany
- Matthias Vorgerd
- Department of Neurology with Heimer Institute for Muscle Research, University Hospital Bergmannsheil, Bochum, Germany
- Beate Brand-Saberi
- Ruhr University Bochum, Medical Faculty, Institute of Anatomy, Department of Anatomy and Molecular Embryology, Bochum, Germany
- Holm Zaehres
- ORCiD
- Ruhr University Bochum, Medical Faculty, Institute of Anatomy, Department of Anatomy and Molecular Embryology, Bochum, Germany; Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology, Münster, Germany
- DOI
- https://doi.org/10.7554/eLife.87081
- Journal volume & issue
-
Vol. 12
Abstract
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.
Keywords
