Detection of all adult Tau isoforms in a 3D culture model of iPSC-derived neurons.
Alginates
/ chemistry
Cell Culture Techniques
/ methods
Cell Line
Cell Lineage
Cerebral Cortex
/ metabolism
Collagen
/ chemistry
Drug Combinations
Humans
Induced Pluripotent Stem Cells
/ cytology
Laminin
/ chemistry
Neurons
/ cytology
Protein Isoforms
/ genetics
Proteoglycans
/ chemistry
tau Proteins
/ genetics
3D culture
Tau
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
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
101541Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.