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Strauß, T.* ; Marvian-Tayaranian, A.* ; Sadikoglou, E.* ; Dhingra, A.* ; Wegner, F.* ; Trümbach, D. ; Wurst, W. ; Heutink, P.* ; Schwarz, S.C.* ; Höglinger, G.U.*

iPS cell-based model for MAPT Haplotype as a risk factor for human tauopathies identifies no major differences in TAU expression.

Front. Cell Dev. Biol. 9:726866 (2021)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The H1 haplotype of the microtubule-associated protein tau (MAPT) gene is a common genetic risk factor for some neurodegenerative diseases such as progressive supranuclear palsy, corticobasal degeneration, and Parkinson’s disease. The molecular mechanism causing the increased risk for the named diseases, however, remains unclear. In this paper, we present a valuable tool of eight small molecule neural precursor cell lines (smNPC) homozygous for the MAPT haplotypes (four H1/H1 and four H2/H2 cell lines), which can be used to identify MAPT-dependent phenotypes. The employed differentiation protocol is fast due to overexpression of NEUROGENIN-2 and therefore suitable for high-throughput approaches. A basic characterization of all human cell lines was performed, and their TAU and α-SYNUCLEIN profiles were compared during a differentiation time of 30 days. We could identify higher levels of conformationally altered TAU in cell lines carrying the H2 haplotype. Additionally, we found increased expression levels of α-SYNUCLEIN in H1/H1 cells. With this resource, we aim to fill a gap in neurodegenerative disease modeling with induced pluripotent stem cells (iPSC) for sporadic tauopathies.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Disease Modeling ; Ipsc ; Mapt Haplotype ; Ngn2 Neurons ; Tau ; α-synuclein; Progressive Supranuclear Palsy; Alpha-synuclein Gene; Mapt H1 Haplotype; Parkinsons-disease; Association Analysis; Protein-tau; Dementia; Snca; Alzheimers; Pathology
ISSN (print) / ISBN 2296-634X
e-ISSN 2296-634X
Journal Frontiers in cell and developmental biology
Quellenangaben Volume: 9, Issue: , Pages: , Article Number: 726866 Supplement: ,
Publisher Frontiers
Publishing Place Lausanne
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Developmental Genetics (IDG)
Grants university library of the Technical University Munich
Petermax-Muller Foundation (Etiology and Therapy of Synucleinopathies and Tauopathies)
VolkswagenStiftung/Lower Saxony Ministry for Science (Niedersachsisches Vorab)
DFG
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy within the Munich Cluster for Systems Neurology
German Federal Ministry of Education and Research