PT  - JOURNAL ARTICLE
AU  - Lampros Mavrommatis
AU  - Hyun-Woo Jeong
AU  - Gemma Gomez-Giro
AU  - Martin Stehling
AU  - Marie-Cécile Kienitz
AU  - Olympia E. Psathaki
AU  - M. Gabriele Bixel
AU  - Gabriela Morosan-Puopolo
AU  - Daniela Gerovska
AU  - Marcos J. Araúzo-Bravo
AU  - Jens C. Schwamborn
AU  - Hans R. Schöler
AU  - Ralf H. Adams
AU  - Matthias Vorgerd
AU  - Beate Brand-Saberi
AU  - Holm Zaehres
TI  - Human skeletal muscle organoids model fetal myogenesis and sustain uncommitted PAX7 myogenic progenitors
AID  - 10.1101/2020.09.14.295832
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.09.14.295832
4099  - http://biorxiv.org/content/early/2020/09/15/2020.09.14.295832.short
4100  - http://biorxiv.org/content/early/2020/09/15/2020.09.14.295832.full
AB  - In vitro culture systems which structurally recapitulate human myogenesis and promote PAX7+ myogenic progenitor maturation have not been established. Here we report human skeletal muscle organoids differentiated from induced pluripotent stem cell lines that contain paraxial mesoderm and neuromesodermal progenitors and develop into organized structures, reassembling neural plate border and dermomyotome formation. Culture conditions cause neural lineage arrest and promote fetal hypaxial myogenesis towards limb axial anatomical identity and generate sustainable uncommitted PAX7 myogenic progenitors, as well as fibroadipogenic (PDGFRa+) progenitor populations equivalent to those from second trimester of human gestation. Single cell comparison to human fetal and adult myogenic progenitors reveals distinct molecular signatures for non-dividing myogenic progenitors in activated (CD44High/CD98+/MYOD1+) and dormant (PAX7High/FBN1High/SPRY1High) states. Our approach, further validated with Duchenne and CRISPR/Cas9 genome-edited Limb-girdle muscular dystrophy (LGMD2A) patient iPSC lines, provides a robust in vitro developmental system for investigating muscle tissue morphogenesis and homeostasis.Competing Interest StatementThe authors have declared no competing interest.