RT Journal Article
SR Electronic
T1 Human skeletal muscle organoids model fetal myogenesis and sustain uncommitted PAX7 myogenic progenitors
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.09.14.295832
DO 10.1101/2020.09.14.295832
A1 Lampros Mavrommatis
A1 Hyun-Woo Jeong
A1 Gemma Gomez-Giro
A1 Martin Stehling
A1 Marie-Cécile Kienitz
A1 Olympia E. Psathaki
A1 M. Gabriele Bixel
A1 Gabriela Morosan-Puopolo
A1 Daniela Gerovska
A1 Marcos J. Araúzo-Bravo
A1 Jens C. Schwamborn
A1 Hans R. Schöler
A1 Ralf H. Adams
A1 Matthias Vorgerd
A1 Beate Brand-Saberi
A1 Holm Zaehres
YR 2021
UL http://biorxiv.org/content/early/2021/01/08/2020.09.14.295832.abstract
AB 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 towards 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 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 novel robust 3D in vitro developmental system for investigating muscle tissue morphogenesis and homeostasis.Competing Interest StatementThe authors have declared no competing interest.