Human induced pluripotent stem cell derived neurons as a model for Williams-Beuren syndrome.
Mol Brain
; 8(1): 77, 2015 Nov 24.
Article
en En
| MEDLINE
| ID: mdl-26603386
ABSTRACT
BACKGROUND:
Williams-Beuren Syndrome (WBS) is caused by the microdeletion of approximately 25 genes on chromosome 7q11.23, and is characterized by a spectrum of cognitive and behavioural features.RESULTS:
We generated cortical neurons from a WBS individual and unaffected (WT) control by directed differentiation of induced pluripotent stem cells (iPSCs). Single cell mRNA analyses and immunostaining demonstrated very efficient production of differentiated cells expressing markers of mature neurons of mixed subtypes and from multiple cortical layers. We found that there was a profound alteration in action potentials, with significantly prolonged WBS repolarization times and a WBS deficit in voltage-activated K(+) currents. Miniature excitatory synaptic currents were normal, indicating that unitary excitatory synaptic transmission was not altered. Gene expression profiling identified 136 negatively enriched gene sets in WBS compared to WT neurons including gene sets involved in neurotransmitter receptor activity, synaptic assembly, and potassium channel complexes.CONCLUSIONS:
Our findings provide insight into gene dysregulation and electrophysiological defects in WBS patient neurons.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Síndrome de Williams
/
Células Madre Pluripotentes Inducidas
/
Modelos Biológicos
/
Neuronas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Mol Brain
Asunto de la revista:
BIOLOGIA MOLECULAR
/
CEREBRO
Año:
2015
Tipo del documento:
Article
País de afiliación:
Canadá