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Although dysfunction of the NMJ causes various neuromuscular diseases, a reliable in vitro system for disease modeling is currently unavailable. Here, we present a potentially novel 2-step, self-organizing approach for generating in vitro human NMJs from human induced pluripotent stem cells. Our simple and robust approach results in a complex NMJ structure that includes functional connectivity, recapitulating in vivo synapse formation. We used these in vitro NMJs to model the pathological features of spinal muscular atrophy, revealing the developmental and functional defects of NMJ formation and NMJ-dependent muscular contraction. Our differentiation system is therefore useful for investigating and understanding the physiology and pathology of human NMJs.<\/jats:p>","DOI":"10.1172\/jci.insight.124299","type":"journal-article","created":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T11:00:55Z","timestamp":1568804455000},"source":"Crossref","is-referenced-by-count":74,"title":["iPSC-derived functional human neuromuscular junctions model the pathophysiology of neuromuscular diseases"],"prefix":"10.1172","volume":"4","author":[{"given":"Chuang-Yu","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4800-8960","authenticated-orcid":true,"given":"Michiko","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Clinical Application, Center for iPS Cell Research and 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