The difficulty to model Huntington's disease in vitro using striatal medium spiny neurons differentiated from human induced pluripotent stem cells.
Action Potentials
Animals
Calcium
/ metabolism
Case-Control Studies
Cell Culture Techniques
Cell Differentiation
Cell Line
Humans
Huntington Disease
Induced Pluripotent Stem Cells
Mice, Inbred C57BL
Neurons
/ physiology
Voltage-Gated Sodium Channel beta-4 Subunit
/ metabolism
gamma-Aminobutyric Acid
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
25 03 2021
25 03 2021
Historique:
received:
07
08
2020
accepted:
03
03
2021
entrez:
26
3
2021
pubmed:
27
3
2021
medline:
28
10
2021
Statut:
epublish
Résumé
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an expanded polyglutamine repeat in the huntingtin gene. The neuropathology of HD is characterized by the decline of a specific neuronal population within the brain, the striatal medium spiny neurons (MSNs). The origins of this extreme vulnerability remain unknown. Human induced pluripotent stem cell (hiPS cell)-derived MSNs represent a powerful tool to study this genetic disease. However, the differentiation protocols published so far show a high heterogeneity of neuronal populations in vitro. Here, we compared two previously published protocols to obtain hiPS cell-derived striatal neurons from both healthy donors and HD patients. Patch-clamp experiments, immunostaining and RT-qPCR were performed to characterize the neurons in culture. While the neurons were mature enough to fire action potentials, a majority failed to express markers typical for MSNs. Voltage-clamp experiments on voltage-gated sodium (Nav) channels revealed a large variability between the two differentiation protocols. Action potential analysis did not reveal changes induced by the HD mutation. This study attempts to demonstrate the current challenges in reproducing data of previously published differentiation protocols and in generating hiPS cell-derived striatal MSNs to model a genetic neurodegenerative disorder in vitro.
Identifiants
pubmed: 33767215
doi: 10.1038/s41598-021-85656-x
pii: 10.1038/s41598-021-85656-x
pmc: PMC7994641
doi:
Substances chimiques
Voltage-Gated Sodium Channel beta-4 Subunit
0
gamma-Aminobutyric Acid
56-12-2
Calcium
SY7Q814VUP
Types de publication
Comparative Study
Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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