Insights into the pathogenesis of ATP1A1-related CMT disease using patient-specific iPSCs.
ATP1A1
Charcot-Marie-Tooth
Na+/K+ ATPase
iPSCs
induced pluripotent stem cells
Journal
Journal of the peripheral nervous system : JPNS
ISSN: 1529-8027
Titre abrégé: J Peripher Nerv Syst
Pays: United States
ID NLM: 9704532
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
22
09
2019
revised:
06
11
2019
accepted:
06
11
2019
pubmed:
11
11
2019
medline:
11
8
2020
entrez:
11
11
2019
Statut:
ppublish
Résumé
The development of patient-specific induced pluripotent stem cells (iPSCs) offered interesting insights in modeling the pathogenesis of Charcot-Marie-Tooth (CMT) disease and thus we decided to explore the phenotypes of iPSCs derived from a single CMT patient carrying a mutant ATP1A1 allele (p.Pro600Ala). iPSCs clones generated from CMT and control fibroblasts, were induced to differentiate into neural precursors and then into post-mitotic neurons. Control iPSCs differentiated into neuronal precursors and then into post-mitotic neurons within 6-8 days. On the contrary, the differentiation of CMT iPSCs was clearly defective. Electrophysiological properties confirmed that post-mitotic neurons were less mature compared to the normal counterpart. The impairment of in vitro differentiation of CMT iPSCs only concerned with the neuronal pathway, because they were able to differentiate into mesendodermal cells and other ectodermal derivatives. ATP1A1 was undetectable in the few neuronal cells derived from CMT iPSCs. ATP1A1 gene mutation (p.Pro600Ala), responsible for a form of axonal CMT disease, is associated in vitro with a dramatic alteration of the differentiation of patient-derived iPSCs into post-mitotic neurons. Thus, the defect in neuronal cell development might lead in vivo to a decreased number of mature neurons in ATP1A1-CMT disease.
Substances chimiques
ATP1A1 protein, human
EC 3.6.1.-
Sodium-Potassium-Exchanging ATPase
EC 7.2.2.13
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
330-339Informations de copyright
© 2019 Peripheral Nerve Society.
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