Decreased nuclear Pten in neural stem cells contributes to deficits in neuronal maturation.
Animals
Autism Spectrum Disorder
/ etiology
Biomarkers
Cell Differentiation
/ genetics
Cell Nucleus
Cell Proliferation
Cell Self Renewal
Cells, Cultured
Disease Models, Animal
Mice
Mice, Knockout
Mutation
Neural Stem Cells
/ cytology
Neurogenesis
/ genetics
Neuroglia
/ cytology
Neurons
/ cytology
PTEN Phosphohydrolase
/ genetics
Autism spectrum disorder
Creb activation
Neural development
Neural stem cells
Neuronal maturation
PTEN mutation
Journal
Molecular autism
ISSN: 2040-2392
Titre abrégé: Mol Autism
Pays: England
ID NLM: 101534222
Informations de publication
Date de publication:
01 06 2020
01 06 2020
Historique:
received:
30
09
2019
accepted:
13
04
2020
entrez:
4
6
2020
pubmed:
4
6
2020
medline:
29
5
2021
Statut:
epublish
Résumé
PTEN, a syndromic autism spectrum disorder (ASD) risk gene, is mutated in approximately 10% of macrocephalic ASD cases. Despite the described genetic association between PTEN and ASD and ensuing studies, we continue to have a limited understanding of how PTEN disruption drives ASD pathogenesis and maintenance. We derived neural stem cells (NSCs) from the dentate gyrus (DG) of Pten The m3m4 mutation decreases Pten localization to the nucleus and its global expression over time. Pten Constitutional disruption of Pten nuclear localization with subsequent global decrease in Pten expression generates abnormal patterns of differentiation, a stunting of neuronal maturation. The propensity of Pten disruption to restrain neurons to a more progenitor-like state may be an important feature contributing to PTEN-ASD pathogenesis.
Sections du résumé
BACKGROUND
PTEN, a syndromic autism spectrum disorder (ASD) risk gene, is mutated in approximately 10% of macrocephalic ASD cases. Despite the described genetic association between PTEN and ASD and ensuing studies, we continue to have a limited understanding of how PTEN disruption drives ASD pathogenesis and maintenance.
METHODS
We derived neural stem cells (NSCs) from the dentate gyrus (DG) of Pten
RESULTS
The m3m4 mutation decreases Pten localization to the nucleus and its global expression over time. Pten
CONCLUSIONS
Constitutional disruption of Pten nuclear localization with subsequent global decrease in Pten expression generates abnormal patterns of differentiation, a stunting of neuronal maturation. The propensity of Pten disruption to restrain neurons to a more progenitor-like state may be an important feature contributing to PTEN-ASD pathogenesis.
Identifiants
pubmed: 32487265
doi: 10.1186/s13229-020-00337-2
pii: 10.1186/s13229-020-00337-2
pmc: PMC7268763
doi:
Substances chimiques
Biomarkers
0
PTEN Phosphohydrolase
EC 3.1.3.67
PTEN protein, human
EC 3.1.3.67
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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