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dc.contributor.authorHuang, Guanqun
dc.contributor.authorChen, Shuting
dc.contributor.authorChen, Xiaoxia
dc.contributor.authorZheng, Jiajun
dc.contributor.authorXu, Zhuoran
dc.contributor.authorDoostparast Torshizi, Abolfazl
dc.contributor.authorGong, Siyi
dc.contributor.authorChen, Qingpei
dc.contributor.authorMa, Xiaokuang
dc.contributor.authorYu, Jiandong
dc.contributor.authorZhou, Libing
dc.contributor.authorQiu, Shenfeng
dc.contributor.authorWang, Kai
dc.contributor.authorShi, Lingling
dc.date.accessioned2019-08-13T23:43:58Z
dc.date.available2019-08-13T23:43:58Z
dc.date.issued2019-03-13
dc.identifier.citationHuang G, Chen S, Chen X, Zheng J, Xu Z, Doostparast Torshizi A, Gong S, Chen Q, Ma X, Yu J, Zhou L, Qiu S, Wang K and Shi L (2019) Uncovering the Functional Link Between SHANK3 Deletions and Deficiency in Neurodevelopment Using iPSC-Derived Human Neurons. Front. Neuroanat. 13:23. doi: 10.3389/fnana.2019.00023en_US
dc.identifier.issn1662-5129
dc.identifier.pmid30918484
dc.identifier.doi10.3389/fnana.2019.00023
dc.identifier.urihttp://hdl.handle.net/10150/633826
dc.description.abstractSHANK3 mutations, including de novo deletions, have been associated with autism spectrum disorders (ASD). However, the effects of SHANK3 loss of function on neurodevelopment remain poorly understood. Here we generated human induced pluripotent stem cells (iPSC) in vitro, followed by neuro-differentiation and lentivirus-mediated shRNA expression to evaluate how SHANK3 knockdown affects the in vitro neurodevelopmental process at multiple time points (up to 4 weeks). We found that SHANK3 knockdown impaired both early stage of neuronal development and mature neuronal function, as demonstrated by a reduction in neuronal soma size, growth cone area, neurite length and branch numbers. Notably, electrophysiology analyses showed defects in excitatory and inhibitory synaptic transmission. Furthermore, transcriptome analyses revealed that multiple biological pathways related to neuron projection, motility and regulation of neurogenesis were disrupted in cells with SHANK3 knockdown. In conclusion, utilizing a human iPSC-based neural induction model, this study presented combined morphological, electrophysiological and transcription evidence that support that SHANK3 as an intrinsic, cell autonomous factor that controls cellular function development in human neurons.en_US
dc.description.sponsorshipNational Natural Science Foundation of China [81771222]; National Key Research and Development Program of China, Stem Cell and Translational Research [2017YFA0105102]; Guangzhou Science and Technology Innovation Development special fund project [201804010212]; Fundamental Research Funds for the Central Universities of China [11617435]; Program of Introducing Talents of Discipline to Universities [B14036]en_US
dc.language.isoenen_US
dc.publisherFRONTIERS MEDIA SAen_US
dc.rights© 2019 Huang, Chen, Chen, Zheng, Xu, Doostparast Torshizi, Gong, Chen, Ma, Yu, Zhou, Qiu, Wang and Shi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en_US
dc.subjectRNA-Seqen_US
dc.subjectSHANK3en_US
dc.subjectautismen_US
dc.subjectelectrophysiologyen_US
dc.subjectinduced pluripotent stem cellsen_US
dc.subjectneural stem cellsen_US
dc.subjecttranscriptomeen_US
dc.titleUncovering the Functional Link Between SHANK3 Deletions and Deficiency in Neurodevelopment Using iPSC-Derived Human Neuronsen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Dept Basic Med Sci, Coll Med Phoenixen_US
dc.identifier.journalFRONTIERS IN NEUROANATOMYen_US
dc.description.noteOpen access journalen_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.journaltitleFrontiers in neuroanatomy
refterms.dateFOA2019-08-13T23:43:58Z


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