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Self-organizing 3D human trunk neuromuscular organoids

Item Type:Article
Title:Self-organizing 3D human trunk neuromuscular organoids
Creators Name:Faustino Martins, J.M. and Fischer, C. and Urzi, A. and Vidal, R. and Kunz, S. and Ruffault, P.L. and Kabuss, L. and Hube, I. and Gazzerro, E. and Birchmeier, C. and Spuler, S. and Sauer, S. and Gouti, M.
Abstract:Neuromuscular networks assemble during early human embryonic development and are essential for the control of body movement. Previous neuromuscular junction modeling efforts using human pluripotent stem cells (hPSCs) generated either spinal cord neurons or skeletal muscles in monolayer culture. Here, we use hPSC-derived axial stem cells, the building blocks of the posterior body, to simultaneously generate spinal cord neurons and skeletal muscle cells that self-organize to generate human neuromuscular organoids (NMOs) that can be maintained in 3D for several months. Single-cell RNA-sequencing of individual organoids revealed reproducibility across experiments and enabled the tracking of the neural and mesodermal differentiation trajectories as organoids developed and matured. NMOs contain functional neuromuscular junctions supported by terminal Schwann cells. They contract and develop central pattern generator-like neuronal circuits. Finally, we successfully use NMOs to recapitulate key aspects of myasthenia gravis pathology, thus highlighting the significant potential of NMOs for modeling neuromuscular diseases in the future.
Keywords:Neuromesodermal Progenitors, NMPs, Neuromuscular Organoids, NMOs, Neuromuscular Diseases, Neuromuscular Junction, Myasthenia Gravis, Central Pattern Generators, Skeletal Muscles, Spinal Cord
Source:Cell Stem Cell
ISSN:1934-5909
Publisher:Cell Press
Volume:26
Number:2
Page Range:172-186.e6
Date:6 February 2020
Official Publication:https://doi.org/10.1016/j.stem.2019.12.007
PubMed:View item in PubMed

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