PT  - JOURNAL ARTICLE
AU  - Elliot W. Swartz
AU  - Greg Shintani
AU  - Jijun Wan
AU  - Joseph S. Maffei
AU  - Sarah H. Wang
AU  - Bruce L. Miller
AU  - Leif A. Havton
AU  - Giovanni Coppola
TI  - Establishment of a Human Induced Pluripotent Stem Cell-Derived Neuromuscular Co-Culture Under Optogenetic Control
AID  - 10.1101/2020.04.10.036400
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.04.10.036400
4099  - http://biorxiv.org/content/early/2020/04/13/2020.04.10.036400.short
4100  - http://biorxiv.org/content/early/2020/04/13/2020.04.10.036400.full
AB  - The failure of the neuromuscular junction (NMJ) is a key component of degenerative neuromuscular disease, yet how NMJs degenerate in disease is unclear. Human induced pluripotent stem cells (hiPSCs) offer the ability to model disease via differentiation toward affected cell types, however, the re-creation of an in vitro neuromuscular system has proven challenging. Here we present a scalable, all-hiPSC-derived co-culture system composed of independently derived spinal motor neurons (MNs) and skeletal myotubes (sKM). In a model of C9orf72-associated disease, co-cultures form functional NMJs that can be manipulated through optical stimulation, eliciting muscle contraction and measurable calcium flux in innervated sKM. Furthermore, co-cultures grown on multi-electrode arrays (MEAs) permit the pharmacological interrogation of neuromuscular physiology. Utilization of this co-culture model as a tunable, patient-derived system may offer significant insights into NMJ formation, maturation, repair, or pathogenic mechanisms that underlie NMJ dysfunction in disease.Competing Interest StatementThe authors have declared no competing interest.