Detection of all adult Tau isoforms in a 3D culture model of iPSC-derived neurons.


Journal

Stem cell research
ISSN: 1876-7753
Titre abrégé: Stem Cell Res
Pays: England
ID NLM: 101316957

Informations de publication

Date de publication:
10 2019
Historique:
received: 15 01 2019
revised: 08 07 2019
accepted: 19 08 2019
pubmed: 16 9 2019
medline: 1 5 2020
entrez: 16 9 2019
Statut: ppublish

Résumé

Tauopathies are a class of neurodegenerative diseases characterized by the presence of pathological intracellular deposits of Tau proteins. Six isoforms of Tau are expressed in the adult human brain, resulting from alternative splicing of the MAPT gene. Tau splicing is developmentally regulated such that only the smallest Tau isoform is expressed in fetal brain, contrary to the adult brain showing the expression of all 6 isoforms. Induced Pluripotent Stem Cell (iPSC) technology has opened up new perspectives in human disease modeling, including tauopathies. However, a major challenge to in vitro recapitulation of Tau pathology in iPSC-derived neurons is their relative immaturity. In this study, we examined the switch in Tau splicing from fetal-only to all adult Tau isoforms during the differentiation of iPSC-derived neurons in a new 3D culture system. First, we showed that iPSC-induced neurons inside Matrigel-coated alginate capsules were able to differentiate into cortical neurons. Then, using a new assay that allowed both the qualitative and the quantitative analysis of all adult MAPT mRNA isoforms individually, we demonstrated that BrainPhys-maintained neurons expressed the 6 adult MAPT mRNA transcripts from 25 weeks of maturation, making this model highly suitable for modeling Tau pathology and therapeutic purposes.

Identifiants

pubmed: 31522011
pii: S1873-5061(19)30171-0
doi: 10.1016/j.scr.2019.101541
pii:
doi:

Substances chimiques

Alginates 0
Drug Combinations 0
Laminin 0
Protein Isoforms 0
Proteoglycans 0
tau Proteins 0
matrigel 119978-18-6
Collagen 9007-34-5

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

101541

Informations de copyright

Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

Auteurs

Laetitia Miguel (L)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and CNR-MAJ, F 76000, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Anne Rovelet-Lecrux (A)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and CNR-MAJ, F 76000, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Maxime Feyeux (M)

Université de Bordeaux, Laboratoire Photonique Numérique et Nanosciences, CNRS UMR 5298, Institut d'Optique, Talence, France.

Thierry Frebourg (T)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and CNR-MAJ, F 76000, Normandy Center for Genomic and Personalized Medicine, Rouen, France; Department of Genetics, Rouen University Hospital, Rouen, France.

Pierre Nassoy (P)

Université de Bordeaux, Laboratoire Photonique Numérique et Nanosciences, CNRS UMR 5298, Institut d'Optique, Talence, France.

Dominique Campion (D)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and CNR-MAJ, F 76000, Normandy Center for Genomic and Personalized Medicine, Rouen, France; Centre Hospitalier du Rouvray, Sotteville-Lès-Rouen, France.

Magalie Lecourtois (M)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and CNR-MAJ, F 76000, Normandy Center for Genomic and Personalized Medicine, Rouen, France. Electronic address: magalie.lecourtois@univ-rouen.fr.

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Classifications MeSH