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http://hdl.handle.net/1942/28504
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DC Field | Value | Language |
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dc.contributor.author | Verheyen, An | - |
dc.contributor.author | Diels, Annick | - |
dc.contributor.author | Reumers, Joke | - |
dc.contributor.author | Van Hoorde, Kirsten | - |
dc.contributor.author | Van den Wyngaert, Ilse | - |
dc.contributor.author | d'Ydewalle, Constantin van Outryve | - |
dc.contributor.author | De Bondt, An | - |
dc.contributor.author | KUIJLAARS, Jacobine | - |
dc.contributor.author | De Muynck, Louis | - |
dc.contributor.author | De Hoogt, Ronald | - |
dc.contributor.author | Bretteville, Alexis | - |
dc.contributor.author | Jaensch, Steffen | - |
dc.contributor.author | Buist, Arjan | - |
dc.contributor.author | Cabrera-Socorro, Alfredo | - |
dc.contributor.author | Wray, Selina | - |
dc.contributor.author | Ebneth, Andreas | - |
dc.contributor.author | Roevens, Peter | - |
dc.contributor.author | Royaux, Ines | - |
dc.contributor.author | Peeters, Pieter J. | - |
dc.date.accessioned | 2019-06-20T10:08:42Z | - |
dc.date.available | 2019-06-20T10:08:42Z | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | STEM CELL REPORTS, 11(2), p. 363-379 | - |
dc.identifier.issn | 2213-6711 | - |
dc.identifier.uri | http://hdl.handle.net/1942/28504 | - |
dc.description.abstract | Tauopathies such as frontotemporal dementia (FTD) remain incurable to date, partially due to the lack of translational in vitro disease models. The MAPT gene, encoding the microtubule-associated protein tau, has been shown to play an important role in FTD pathogenesis. Therefore, we used zinc finger nucleases to introduce two MAPT mutations into healthy donor induced pluripotent stem cells (iPSCs). The IVS10+16 mutation increases the expression of 4R tau, while the P301S mutation is pro-aggregant. Whole-transcriptome analysis of MAPT IVS10+16 neurons reveals neuronal subtype differences, reduced neural progenitor proliferation potential, and aberrant WNT/SHH signaling. Notably, these neurodevelopmental phenotypes could be recapitulated in neurons from patients carrying the MAPT IVS10+16 mutation. Moreover, the additional pro-aggregant P301S mutation revealed additional phenotypes, such as an increased calcium burst frequency, reduced lysosomal acidity, tau oligomerization, and neurodegeneration. This series of iPSCs could serve as a platform to unravel a potential link between pathogenic 4R tau and FTD. | - |
dc.description.sponsorship | The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreements number 115439 (StemBANCC) and 115582 (EBiSC), resources of which are composed of financial contributions from the European Union's Seventh Framework Program (FP7/2007-2013) and EFPIA companies' in-kind contribution. This publication reflects only the author's views, and neither the IMI JU nor EFPIA nor the European Commission is liable for any use that may be made of the information contained therein. We would like to thank Jason Gustin and Mark Gerber from Sigma-Aldrich for the generation of all gene-edited (ZFN) MAPT lines and Sjors Den Boer for technical assistance. Authors A.V., A.D., J.R., I.V.d.W., C.v.O. d'Y., A.D.B., L.D.M., R.D.H., A. Bretteville, S.J., A. Buist, A.C.S., A.E., P.R., I.R., and P.J.P. are employees of Janssen Pharmaceutica N.V. | - |
dc.language.iso | en | - |
dc.publisher | CELL PRESS | - |
dc.rights | 2018 The Author(s).This is an open access article under the CC BY license | - |
dc.title | Genetically Engineered iPSC-Derived FTDP-17 MAPT Neurons Display Mutation-Specific Neurodegenerative and Neurodevelopmental Phenotypes | - |
dc.type | Journal Contribution | - |
dc.identifier.epage | 379 | - |
dc.identifier.issue | 2 | - |
dc.identifier.spage | 363 | - |
dc.identifier.volume | 11 | - |
local.format.pages | 17 | - |
local.bibliographicCitation.jcat | A1 | - |
dc.description.notes | [Verheyen, An; Diels, Annick; Reumers, Joke; Van den Wyngaert, Ilse; d'Ydewalle, Constantin van Outryve; De Bondt, An; De Muynck, Louis; De Hoogt, Ronald; Bretteville, Alexis; Jaensch, Steffen; Buist, Arjan; Cabrera-Socorro, Alfredo; Ebneth, Andreas; Roevens, Peter; Royaux, Ines; Peeters, Pieter J.] Janssen Res & Dev, Turnhoutseweg 30, B-2340 Beerse, Belgium. [Van Hoorde, Kirsten] Open Analyt NV, B-2600 Antwerp, Belgium. [Kuijlaars, Jacobine] Hasselt Univ, Biomed Res Inst, B-3590 Diepenbeek, Belgium. [Wray, Selina] UCL, Inst Neurol, Dept Mol Neurosci, London WC1N 1PJ, England. | - |
local.publisher.place | CAMBRIDGE | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
dc.identifier.doi | 10.1016/j.stemcr.2018.06.022 | - |
dc.identifier.isi | 000441583100007 | - |
item.validation | ecoom 2019 | - |
item.contributor | Verheyen, An | - |
item.contributor | Diels, Annick | - |
item.contributor | Reumers, Joke | - |
item.contributor | Van Hoorde, Kirsten | - |
item.contributor | Van den Wyngaert, Ilse | - |
item.contributor | d'Ydewalle, Constantin van Outryve | - |
item.contributor | De Bondt, An | - |
item.contributor | KUIJLAARS, Jacobine | - |
item.contributor | De Muynck, Louis | - |
item.contributor | De Hoogt, Ronald | - |
item.contributor | Bretteville, Alexis | - |
item.contributor | Jaensch, Steffen | - |
item.contributor | Buist, Arjan | - |
item.contributor | Cabrera-Socorro, Alfredo | - |
item.contributor | Wray, Selina | - |
item.contributor | Ebneth, Andreas | - |
item.contributor | Roevens, Peter | - |
item.contributor | Royaux, Ines | - |
item.contributor | Peeters, Pieter J. | - |
item.accessRights | Open Access | - |
item.fullcitation | Verheyen, An; Diels, Annick; Reumers, Joke; Van Hoorde, Kirsten; Van den Wyngaert, Ilse; d'Ydewalle, Constantin van Outryve; De Bondt, An; KUIJLAARS, Jacobine; De Muynck, Louis; De Hoogt, Ronald; Bretteville, Alexis; Jaensch, Steffen; Buist, Arjan; Cabrera-Socorro, Alfredo; Wray, Selina; Ebneth, Andreas; Roevens, Peter; Royaux, Ines & Peeters, Pieter J. (2018) Genetically Engineered iPSC-Derived FTDP-17 MAPT Neurons Display Mutation-Specific Neurodegenerative and Neurodevelopmental Phenotypes. In: STEM CELL REPORTS, 11(2), p. 363-379. | - |
item.fulltext | With Fulltext | - |
crisitem.journal.issn | 2213-6711 | - |
crisitem.journal.eissn | 2213-6711 | - |
Appears in Collections: | Research publications |
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verheyen 1.pdf | Published version | 7.04 MB | Adobe PDF | View/Open |
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