{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T20:46:38Z","timestamp":1785530798567,"version":"3.56.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,10,23]],"date-time":"2017-10-23T00:00:00Z","timestamp":1508716800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,10,23]],"date-time":"2017-10-23T00:00:00Z","timestamp":1508716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Integration of stem cell-derived cells into native cellular environment remains a challenge in the field. This study developed novel methods to co-culture neural stem cell-derived spiral ganglion-like neurons (ScNs) and mouse auditory cochlear nucleus (CN) neurons to understand whether ScNs of the peripheral nervous system (PNS) synapse with CN neurons of the central nervous system (CNS). ScNs were obtained from neural stem cells that were derived from transgenic mouse pre-labeled with enhanced green fluorescent protein (EGFP), whereas CN neurons were from postnatal mouse primary cultures. ScNs and CN neurons were co-cultured\u00a0 for 4\u20136 days in the absence or presence of astrocyte-conditioned medium (ACM). Class III \u03b2-tubulin (TUJ1)-expressing connections were found between ScNs and CN neurons. Expression of the synaptic vesicle marker SV2 was significantly increased along connections between ScNs and CN neurons in the presence of ACM. Immunodepletion and knockout studies indicated that thrombospodin-1 played an important role in ACM-exerted synaptogenic effects. Newly-generated synapse-like structures expressed glutamatergic marker VGluT1, pre- and post-synaptic proteins. Synaptic vesicle recycling studies suggested functional synaptic vesicle retrieval. These results reveal that stem cell-derived PNS neurons are able to form functional connections with native CNS neurons, which is critical for stem cell-based neural pathway regeneration.<\/jats:p>","DOI":"10.1038\/s41598-017-13764-8","type":"journal-article","created":{"date-parts":[[2017,10,17]],"date-time":"2017-10-17T15:24:34Z","timestamp":1508253874000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Stimulation of synapse formation between stem cell-derived neurons and native brainstem auditory neurons"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2975-8635","authenticated-orcid":false,"given":"Zhengqing","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenjie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,10,23]]},"reference":[{"key":"13764_CR1","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.heares.2007.12.005","volume":"242","author":"RK Shepherd","year":"2008","unstructured":"Shepherd, R. K., Coco, A. & Epp, S. B. Neurotrophins and electrical stimulation for protection and repair of spiral ganglion neurons following sensorineural hearing loss. Hear Res \n                           242, 100\u2013109, https:\/\/doi.org\/10.1016\/j.heares.2007.12.005 (2008).","journal-title":"Hear Res"},{"key":"13764_CR2","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1007\/s10162-009-0170-2","volume":"10","author":"MJ Agterberg","year":"2009","unstructured":"Agterberg, M. J., Versnel, H., van Dijk, L. M., de Groot, J. C. & Klis, S. F. Enhanced survival of spiral ganglion cells after cessation of treatment with brain-derived neurotrophic factor in deafened guinea pigs. 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Thrombospondins as key regulators of synaptogenesis in the central nervous system. Matrix Biol \n                           31, 170-177, doi:10.1016\/j.matbio.2012.01.004 (2012).","DOI":"10.1016\/j.matbio.2012.01.004"},{"key":"13764_CR18","doi-asserted-by":"publisher","first-page":"2227","DOI":"10.1046\/j.1471-4159.1999.0732227.x","volume":"73","author":"MA Cousin","year":"1999","unstructured":"Cousin, M. A. & Robinson, P. J. Mechanisms of synaptic vesicle recycling illuminated by fluorescent dyes. J Neurochem \n                           73, 2227\u20132239 (1999).","journal-title":"J Neurochem"},{"key":"13764_CR19","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1002\/embj.201386357","volume":"33","author":"SO Rizzoli","year":"2014","unstructured":"Rizzoli, S. O. Synaptic vesicle recycling: steps and principles. 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