Establishment of a Human Induced Pluripotent Stem Cell-Derived Neuromuscular Co-Culture Under Optogenetic Control
Establishment of a Human Induced Pluripotent Stem Cell-Derived Neuromuscular Co-Culture Under Optogenetic Control
Summary 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.
Swartz Elliot W.、Shintani Greg、Maffei Joseph S.、Wang Sarah H.、Miller Bruce L.、Coppola Giovanni、Wan Jijun、Havton Leif A.
Semel Institute for Neuroscience and Human Behavior, University of California||Department of Psychiatry and Biobehavioral Sciences, University of California||Neuroscience Interdepartmental Program, University of CaliforniaSemel Institute for Neuroscience and Human Behavior, University of California||Department of Psychiatry and Biobehavioral Sciences, University of CaliforniaAxion BiosystemsSemel Institute for Neuroscience and Human Behavior, University of CaliforniaMemory and Aging Center, University of California, San FranciscoSemel Institute for Neuroscience and Human Behavior, University of California||Department of Psychiatry and Biobehavioral Sciences, University of California||Neuroscience Interdepartmental Program, University of California||Department of Neurology, University of CaliforniaSemel Institute for Neuroscience and Human Behavior, University of California||Department of Psychiatry and Biobehavioral Sciences, University of CaliforniaDepartment of Neurobiology, David Geffen School of Medicine at UCLA, University of California
基础医学神经病学、精神病学生物科学研究方法、生物科学研究技术
iPSCsskeletal myotubemotor neuronoptogeneticsmulti-electrode arrayneuromuscularco-cultureC9orf72
Swartz Elliot W.,Shintani Greg,Maffei Joseph S.,Wang Sarah H.,Miller Bruce L.,Coppola Giovanni,Wan Jijun,Havton Leif A..Establishment of a Human Induced Pluripotent Stem Cell-Derived Neuromuscular Co-Culture Under Optogenetic Control[EB/OL].(2025-03-28)[2025-05-13].https://www.biorxiv.org/content/10.1101/2020.04.10.036400.点此复制
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