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dc.contributor.authorNayler, SP
dc.contributor.authorPowell, JE
dc.contributor.authorVanichkina, DP
dc.contributor.authorKorn, O
dc.contributor.authorWells, CA
dc.contributor.authorKanjhan, R
dc.contributor.authorSun, J
dc.contributor.authorTaft, RJ
dc.contributor.authorLavin, MF
dc.contributor.authorWolvetang, EJ
dc.date.accessioned2020-12-21T04:01:58Z
dc.date.available2020-12-21T04:01:58Z
dc.date.issued2017-10-13
dc.identifier.citationNayler, S. P., Powell, J. E., Vanichkina, D. P., Korn, O., Wells, C. A., Kanjhan, R., Sun, J., Taft, R. J., Lavin, M. F. & Wolvetang, E. J. (2017). Human iPSC-Derived Cerebellar Neurons from a Patient with Ataxia-Telangiectasia Reveal Disrupted Gene Regulatory Networks. FRONTIERS IN CELLULAR NEUROSCIENCE, 11, https://doi.org/10.3389/fncel.2017.00321.
dc.identifier.issn1662-5102
dc.identifier.urihttp://hdl.handle.net/11343/257455
dc.description.abstractAtaxia-telangiectasia (A-T) is a rare genetic disorder caused by loss of function of the ataxia-telangiectasia-mutated kinase and is characterized by a predisposition to cancer, pulmonary disease, immune deficiency and progressive degeneration of the cerebellum. As animal models do not faithfully recapitulate the neurological aspects, it remains unclear whether cerebellar degeneration is a neurodevelopmental or neurodegenerative phenotype. To address the necessity for a human model, we first assessed a previously published protocol for the ability to generate cerebellar neuronal cells, finding it gave rise to a population of precursors highly enriched for markers of the early hindbrain such as EN1 and GBX2, and later more mature cerebellar markers including PTF1α, MATH1, HOXB4, ZIC3, PAX6, and TUJ1. RNA sequencing was used to classify differentiated cerebellar neurons generated from integration-free A-T and control induced pluripotent stem cells. Comparison of RNA sequencing data with datasets from the Allen Brain Atlas reveals in vitro-derived cerebellar neurons are transcriptionally similar to discrete regions of the human cerebellum, and most closely resemble the cerebellum at 22 weeks post-conception. We show that patient-derived cerebellar neurons exhibit disrupted gene regulatory networks associated with synaptic vesicle dynamics and oxidative stress, offering the first molecular insights into early cerebellar pathogenesis of ataxia-telangiectasia.
dc.languageEnglish
dc.publisherFRONTIERS MEDIA SA
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleHuman iPSC-Derived Cerebellar Neurons from a Patient with Ataxia-Telangiectasia Reveal Disrupted Gene Regulatory Networks
dc.typeJournal Article
dc.identifier.doi10.3389/fncel.2017.00321
melbourne.affiliation.departmentAnatomy and Neuroscience
melbourne.source.titleFrontiers in Cellular Neuroscience
melbourne.source.volume11
dc.rights.licenseCC BY
melbourne.elementsid1271664
melbourne.contributor.authorWells, Christine
dc.identifier.eissn1662-5102
melbourne.accessrightsOpen Access


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