RT Journal Article
T1 Generation of a human induced pluripotent stem cell-based model for tauopathies combining three microtubule-associated protein TAU mutations which displays several phenotypes linked to neurodegeneration
A1 García-León, Juan Antonio
A1 Cabrera-Socorro, Alfredo
A1 Eggermont, Kristel
A1 Swijsen, Ann
A1 Terryn, Joke
A1 Fazal, Raheem
A1 Nami, FatemehArefeh
A1 Ordovás, Laura
A1 Quiles, Ana
A1 Lluis, Frederic
A1 Serneels, Lutgarde
A1 Wierda, Keimpe
A1 Sierksma, Annerieke
A1 Kreir, Mohamed
A1 Pestana, Francisco
A1 Van Damme, Philip
A1 De Strooper, Bart
A1 Thorrez, Lieven
A1 Ebneth, Andreas
A1 Verfaillie, Catherine M
K1 Alzheimer, Enfermedad de
AB IntroductionTauopathies are neurodegenerative diseases characterized by TAU protein–related pathology, including frontotemporal dementia and Alzheimer's disease among others. Mutant TAU animal models are available, but none of them faithfully recapitulates human pathology and are not suitable for drug screening.MethodsTo create a new in vitro tauopathy model, we generated a footprint-free triple MAPT-mutant human induced pluripotent stem cell line (N279K, P301L, and E10+16 mutations) using clustered regularly interspaced short palindromic repeats-FokI and piggyBac transposase technology.ResultsMutant neurons expressed pathogenic 4R and phosphorylated TAU, endogenously triggered TAU aggregation, and had increased electrophysiological activity. TAU-mutant cells presented deficiencies in neurite outgrowth, aberrant sequence of differentiation to cortical neurons, and a significant activation of stress response pathways. RNA sequencing confirmed stress activation, demonstrated a shift toward GABAergic identity, and an upregulation of neurodegenerative pathways.DiscussionIn summary, we generated a novel in vitro human induced pluripotent stem cell TAU-mutant model displaying neurodegenerative disease phenotypes that could be used for disease modeling and drug screening.
PB Wiley
YR 2018
FD 2018-10
LK https://hdl.handle.net/10630/34483
UL https://hdl.handle.net/10630/34483
LA eng
NO Juan Antonio García-León, Alfredo Cabrera-Socorro, Kristel Eggermont, Ann Swijsen, Joke Terryn, Raheem Fazal, FatemehArefeh Nami, Laura Ordovás, Ana Quiles, Frederic Lluis, Lutgarde Serneels, Keimpe Wierda, Annerieke Sierksma, Mohamed Kreir, Francisco Pestana, Philip Van Damme, Bart De Strooper, Lieven Thorrez, Andreas Ebneth, Catherine M Verfaillie. Generation of a human induced pluripotent stem cell-based model for tauopathies combining three microtubule-associated protein TAU mutations which displays several phenotypes linked to neurodegeneration. Alzheimers Dement . 2018 Oct;14(10):1261-1280. doi: 10.1016/j.jalz.2018.05.007. Epub 2018 Jul 20.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 4 mar 2026