{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T20:49:07Z","timestamp":1785530947285,"version":"3.56.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Veterans Affairs Merit Grant"},{"DOI":"10.13039\/100006710","name":"Wayne State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Human Cell"],"DOI":"10.1007\/s13577-025-01194-y","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T03:28:26Z","timestamp":1741750106000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["In vitro generation of spiral ganglion neurons from embryonic stem cells"],"prefix":"10.1007","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8913-1688","authenticated-orcid":false,"given":"Oluwafemi S.","family":"Agboola","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2975-8635","authenticated-orcid":false,"given":"Zhengqing","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,12]]},"reference":[{"issue":"30","key":"1194_CR1","doi-asserted-by":"publisher","first-page":"10903","DOI":"10.1523\/JNEUROSCI.2358-11.2011","volume":"31","author":"CC Lu","year":"2011","unstructured":"Lu CC, et al. Developmental profiling of spiral ganglion neurons reveals insights into auditory circuit assembly. J Neurosci. 2011;31(30):10903\u201318.","journal-title":"J Neurosci"},{"issue":"4","key":"1194_CR2","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1016\/j.pneurobio.2011.01.004","volume":"93","author":"JM Appler","year":"2011","unstructured":"Appler JM, Goodrich LV. Connecting the ear to the brain: Molecular mechanisms of auditory circuit assembly. Prog Neurobiol. 2011;93(4):488\u2013508.","journal-title":"Prog Neurobiol"},{"issue":"5","key":"1194_CR3","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1016\/j.cell.2018.07.008","volume":"174","author":"S Sun","year":"2018","unstructured":"Sun S, et al. Hair cell mechanotransduction regulates spontaneous activity and spiral ganglion subtype specification in the auditory system. Cell. 2018;174(5):1247-1263.e15.","journal-title":"Cell"},{"issue":"48","key":"1194_CR4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2203935119","volume":"119","author":"TR Sanders","year":"2022","unstructured":"Sanders TR. Specification of neuronal subtypes in the spiral ganglion begins prior to birth in the mouse. Proc Natl Acad Sci U S A. 2022;119(48): e2203935119.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"1194_CR5","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1097\/MOO.0000000000000748","volume":"29","author":"S Sun","year":"2021","unstructured":"Sun S, Siebald C, M\u00fcller U. Subtype maturation of spiral ganglion neurons. Curr Opin Otolaryngol Head Neck Surg. 2021;29(5):391\u20139.","journal-title":"Curr Opin Otolaryngol Head Neck Surg"},{"issue":"5","key":"1194_CR6","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1016\/j.semcdb.2013.04.003","volume":"24","author":"TM Coate","year":"2013","unstructured":"Coate TM, Kelley MW. Making connections in the inner ear: recent insights into the development of spiral ganglion neurons and their connectivity with sensory hair cells. Semin Cell Dev Biol. 2013;24(5):460\u20139.","journal-title":"Semin Cell Dev Biol"},{"issue":"19","key":"1194_CR7","doi-asserted-by":"publisher","first-page":"7509","DOI":"10.1523\/JNEUROSCI.5138-14.2015","volume":"35","author":"KA Fernandez","year":"2015","unstructured":"Fernandez KA, et al. Aging after noise exposure: acceleration of cochlear synaptopathy in recovered ears. J Neurosci. 2015;35(19):7509\u201320.","journal-title":"J Neurosci"},{"key":"1194_CR8","first-page":"1","volume":"222","author":"M Lethbridge-Cejku","year":"2004","unstructured":"Lethbridge-Cejku M, Schiller JS, Bernadel L. 2002 Summary health statistics for US adults: National Health Interview Survey. Vital Health Stat. 2004;222:1\u2013151.","journal-title":"Vital Health Stat"},{"issue":"12","key":"1194_CR9","doi-asserted-by":"publisher","first-page":"1967","DOI":"10.1002\/cne.24867","volume":"528","author":"PM Brooks","year":"2020","unstructured":"Brooks PM, et al. Pou3f4-expressing otic mesenchyme cells promote spiral ganglion neuron survival in the postnatal mouse cochlea. J Comp Neurol. 2020;528(12):1967\u201385.","journal-title":"J Comp Neurol"},{"issue":"4","key":"1194_CR10","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/j.bbrc.2020.07.101","volume":"532","author":"YF Cheng","year":"2020","unstructured":"Cheng YF, et al. Generation and pathological characterization of a transgenic mouse model carrying a missense PJVK mutation. Biochem Biophys Res Commun. 2020;532(4):675\u201381.","journal-title":"Biochem Biophys Res Commun"},{"issue":"29","key":"1194_CR11","doi-asserted-by":"publisher","first-page":"7740","DOI":"10.1523\/JNEUROSCI.0554-16.2016","volume":"36","author":"M Perny","year":"2016","unstructured":"Perny M, et al. The severity of infection determines the localization of damage and extent of sensorineural hearing loss in experimental pneumococcal meningitis. J Neurosci. 2016;36(29):7740\u20139.","journal-title":"J Neurosci"},{"key":"1194_CR12","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.neuroscience.2019.05.012","volume":"410","author":"C Carignano","year":"2019","unstructured":"Carignano C, et al. Inner hair cell and neuron degeneration contribute to hearing loss in a DFNA2-like mouse model. Neuroscience. 2019;410:202\u201316.","journal-title":"Neuroscience"},{"key":"1194_CR13","doi-asserted-by":"publisher","first-page":"4439","DOI":"10.1523\/JNEUROSCI.3238-20.2021","volume":"41","author":"PZ Wu","year":"2021","unstructured":"Wu PZ, et al. Primary neural degeneration in noise-exposed human cochleas: correlations with outer hair cell loss and word-discrimination scores. J Neurosci. 2021;41:4439\u201347.","journal-title":"J Neurosci"},{"key":"1194_CR14","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.761847","volume":"9","author":"Z Hu","year":"2021","unstructured":"Hu Z, et al. Generation of a spiral ganglion neuron degeneration mouse model. Front Cell Dev Biol. 2021;9: 761847.","journal-title":"Front Cell Dev Biol"},{"key":"1194_CR15","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2021.814891","volume":"15","author":"L Zhang","year":"2021","unstructured":"Zhang L, Chen S, Sun Y. Mechanism and prevention of spiral ganglion neuron degeneration in the cochlea. Front Cell Neurosci. 2021;15: 814891.","journal-title":"Front Cell Neurosci"},{"key":"1194_CR16","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2021.829564","volume":"14","author":"M Wang","year":"2021","unstructured":"Wang M, et al. Regulation of spiral ganglion neuron regeneration as a therapeutic strategy in sensorineural hearing loss. Front Mol Neurosci. 2021;14: 829564.","journal-title":"Front Mol Neurosci"},{"issue":"8","key":"1194_CR17","doi-asserted-by":"publisher","first-page":"1446","DOI":"10.1097\/MAO.0000000000000443","volume":"35","author":"SM Viana","year":"2014","unstructured":"Viana SM, LM. and Nadol Jr JB. Within-subject comparison of word recognition and spiral ganglion cell count in bilateral cochlear implant recipients. Otol Neurotol. 2014;35(8):1446\u201350.","journal-title":"Otol Neurotol"},{"issue":"8","key":"1194_CR18","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1097\/01.mlg.0000227176.09500.28","volume":"116","author":"JN Fayad","year":"2006","unstructured":"Fayad JN, Linthicum FH Jr. Multichannel cochlear implants: relation of histopathology to performance. Laryngoscope. 2006;116(8):1310\u201320.","journal-title":"Laryngoscope"},{"key":"1194_CR19","doi-asserted-by":"publisher","first-page":"409","DOI":"10.3389\/fncel.2017.00409","volume":"11","author":"M Perny","year":"2017","unstructured":"Perny M, et al. Generation of Otic sensory neurons from mouse embryonic stem cells in 3D culture. Front Cell Neurosci. 2017;11:409.","journal-title":"Front Cell Neurosci"},{"issue":"9","key":"1194_CR20","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1038\/nn1301","volume":"7","author":"M Bibel","year":"2004","unstructured":"Bibel M, et al. Differentiation of mouse embryonic stem cells into a defined neuronal lineage. Nat Neurosci. 2004;7(9):1003\u20139.","journal-title":"Nat Neurosci"},{"issue":"1","key":"1194_CR21","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.stemcr.2018.05.006","volume":"11","author":"Z Liu","year":"2018","unstructured":"Liu Z, et al. Embryonic stem cell-derived peripheral auditory neurons form neural connections with mouse central auditory neurons in vitro via the \u03b12\u03b41 receptor. Stem Cell Reports. 2018;11(1):157\u201370.","journal-title":"Stem Cell Reports"},{"key":"1194_CR22","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/S0079-6123(03)46017-2","volume":"146","author":"B Fritzsch","year":"2004","unstructured":"Fritzsch B, et al. Neurotrophins in the ear: their roles in sensory neuron survival and fiber guidance. Prog Brain Res. 2004;146:265\u201378.","journal-title":"Prog Brain Res"},{"issue":"3","key":"1194_CR23","doi-asserted-by":"publisher","first-page":"294","DOI":"10.2174\/1570159X13666150403231920","volume":"13","author":"L Aloe","year":"2015","unstructured":"Aloe L, et al. Nerve Growth factor: a focus on neuroscience and therapy. Curr Neuropharmacol. 2015;13(3):294\u2013303.","journal-title":"Curr Neuropharmacol"},{"issue":"3","key":"1194_CR24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092157","volume":"9","author":"K Kranz","year":"2014","unstructured":"Kranz K, et al. Phosphodiesterase type 4 inhibitor rolipram improves survival of spiral ganglion neurons in vitro. PLoS ONE. 2014;9(3): e92157.","journal-title":"PLoS ONE"},{"issue":"1","key":"1194_CR25","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.brainres.2004.08.013","volume":"1026","author":"Z Hu","year":"2004","unstructured":"Hu Z, Ulfendahl M, Olivius NP. Central migration of neuronal tissue and embryonic stem cells following transplantation along the adult auditory nerve. Brain Res. 2004;1026(1):68\u201373.","journal-title":"Brain Res"},{"key":"1194_CR26","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21228649","author":"X Deng","year":"2020","unstructured":"Deng X, Hu Z. Generation of cochlear hair cells from Sox2 Positive supporting cells via DNA demethylation. Int J Mol Sci. 2020. https:\/\/doi.org\/10.3390\/ijms21228649.","journal-title":"Int J Mol Sci"},{"issue":"1","key":"1194_CR27","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/0165-3806(95)00198-0","volume":"92","author":"H Staecker","year":"1996","unstructured":"Staecker H, et al. NGF, BDNF and NT-3 play unique roles in the in vitro development and patterning of innervation of the mammalian inner ear. Dev Brain Res. 1996;92(1):49\u201360.","journal-title":"Dev Brain Res"},{"issue":"1","key":"1194_CR28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0170568","volume":"12","author":"K Nishimura","year":"2017","unstructured":"Nishimura K, Noda T, Dabdoub A. Dynamic expression of Sox2, Gata3, and Prox1 during primary auditory neuron development in the mammalian cochlea. PLoS ONE. 2017;12(1): e0170568.","journal-title":"PLoS ONE"},{"issue":"6","key":"1194_CR29","doi-asserted-by":"publisher","first-page":"1766","DOI":"10.1002\/term.2072","volume":"11","author":"M Ishikawa","year":"2017","unstructured":"Ishikawa M, et al. Transplantation of neurons derived from human iPS cells cultured on collagen matrix into guinea-pig cochleae. J Tissue Eng Regen Med. 2017;11(6):1766\u201378.","journal-title":"J Tissue Eng Regen Med"},{"issue":"34","key":"1194_CR30","doi-asserted-by":"publisher","first-page":"13686","DOI":"10.1523\/JNEUROSCI.1783-13.2013","volume":"33","author":"Y Sergeyenko","year":"2013","unstructured":"Sergeyenko Y, et al. Age-related cochlear synaptopathy: an early-onset contributor to auditory functional decline. J Neurosci. 2013;33(34):13686.","journal-title":"J Neurosci"},{"key":"1194_CR31","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.neuroscience.2018.07.053","volume":"407","author":"PZ Wu","year":"2019","unstructured":"Wu PZ, et al. Primary neural degeneration in the human cochlea: evidence for hidden hearing loss in the aging Ear. Neuroscience. 2019;407:8\u201320.","journal-title":"Neuroscience"},{"issue":"1","key":"1194_CR32","doi-asserted-by":"publisher","first-page":"5341","DOI":"10.1038\/s41467-023-40803-y","volume":"14","author":"G Vainorius","year":"2023","unstructured":"Vainorius G, et al. Ascl1 and Ngn2 convert mouse embryonic stem cells to neurons via functionally distinct paths. Nat Commun. 2023;14(1):5341.","journal-title":"Nat Commun"},{"issue":"10","key":"1194_CR33","doi-asserted-by":"publisher","first-page":"1454","DOI":"10.1038\/nprot.2009.157","volume":"4","author":"N Gaspard","year":"2009","unstructured":"Gaspard N, et al. Generation of cortical neurons from mouse embryonic stem cells. Nat Protoc. 2009;4(10):1454\u201363.","journal-title":"Nat Protoc"},{"issue":"5","key":"1194_CR34","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1083\/jcb.149.5.1011","volume":"149","author":"GV Putcha","year":"2000","unstructured":"Putcha GV, Deshmukh M, Johnson EM Jr. Inhibition of apoptotic signaling cascades causes loss of trophic factor dependence during neuronal maturation. J Cell Biol. 2000;149(5):1011\u20138.","journal-title":"J Cell Biol"},{"issue":"4","key":"1194_CR35","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1002\/neu.1036","volume":"47","author":"N Orike","year":"2001","unstructured":"Orike N, et al. Differential regulation of survival and growth in adult sympathetic neurons: an in vitro study of neurotrophin responsiveness. J Neurobiol. 2001;47(4):295\u2013305.","journal-title":"J Neurobiol"},{"issue":"40","key":"1194_CR36","doi-asserted-by":"publisher","first-page":"15940","DOI":"10.1523\/JNEUROSCI.0928-13.2013","volume":"33","author":"P Fontanet","year":"2013","unstructured":"Fontanet P, et al. Pea3 transcription factor family members Etv4 and Etv5 mediate retrograde signaling and axonal growth of DRG sensory neurons in response to NGF. J Neurosci. 2013;33(40):15940\u201351.","journal-title":"J Neurosci"},{"issue":"27","key":"1194_CR37","doi-asserted-by":"publisher","first-page":"5284","DOI":"10.1523\/JNEUROSCI.2728-18.2019","volume":"39","author":"HE Sherrill","year":"2019","unstructured":"Sherrill HE, et al. Pou4f1 defines a subgroup of type I spiral ganglion neurons and is necessary for normal inner hair cell presynaptic Ca(2+) signaling. J Neurosci. 2019;39(27):5284\u201398.","journal-title":"J Neurosci"},{"issue":"1","key":"1194_CR38","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.gep.2014.03.001","volume":"15","author":"M Deng","year":"2014","unstructured":"Deng M, et al. Comparative expression analysis of POU4F1, POU4F2 and ISL1 in developing mouse cochleovestibular ganglion neurons. Gene Expr Patterns. 2014;15(1):31\u20137.","journal-title":"Gene Expr Patterns"},{"key":"1194_CR39","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21207777","author":"L Colucci-D'Amato","year":"2020","unstructured":"Colucci-D\u2019Amato L, Speranza L, Volpicelli F. Neurotrophic factor BDNF, physiological functions and therapeutic potential in depression, neurodegeneration and brain cancer. Int J Mol Sci. 2020. https:\/\/doi.org\/10.3390\/ijms21207777.","journal-title":"Int J Mol Sci"},{"key":"1194_CR40","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.actbio.2016.11.030","volume":"49","author":"S Kandalam","year":"2017","unstructured":"Kandalam S, et al. Pharmacologically active microcarriers delivering BDNF within a hydrogel: novel strategy for human bone marrow-derived stem cells neural\/neuronal differentiation guidance and therapeutic secretome enhancement. Acta Biomater. 2017;49:167\u201380.","journal-title":"Acta Biomater"},{"issue":"6","key":"1194_CR41","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1038\/nrneurol.2009.54","volume":"5","author":"C Zuccato","year":"2009","unstructured":"Zuccato C, Cattaneo E. Brain-derived neurotrophic factor in neurodegenerative diseases. Nat Rev Neurol. 2009;5(6):311\u201322.","journal-title":"Nat Rev Neurol"}],"container-title":["Human Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13577-025-01194-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13577-025-01194-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13577-025-01194-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T19:04:11Z","timestamp":1746731051000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13577-025-01194-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,12]]},"references-count":41,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["1194"],"URL":"https:\/\/doi.org\/10.1007\/s13577-025-01194-y","relation":{},"ISSN":["1749-0774"],"issn-type":[{"value":"1749-0774","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,12]]},"assertion":[{"value":"20 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no competing financial interests related to the research presented in this manuscript. All research was conducted independently, and no external funding sources influenced the study design, data analysis, or interpretation of results.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Not applicable to this manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable to this manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"O.S.A, M.D and Z.H. give consent for publication of this manuscript.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"68"}}