iPSC-derived neurons of CREBBP- and EP300-mutated Rubinstein-Taybi syndrome patients show morphological alterations and hypoexcitability.
Stem Cell Res
; 30: 130-140, 2018 07.
Article
em En
| MEDLINE
| ID: mdl-29883886
ABSTRACT
Rubinstein-Taybi syndrome (RSTS) is a rare neurodevelopmental disorder characterized by distinctive facial features, growth retardation, broad thumbs and toes and mild to severe intellectual disability, caused by heterozygous mutations in either CREBBP or EP300 genes, encoding the homologous CBP and p300 lysine-acetyltransferases and transcriptional coactivators. No RSTS in vitro induced Pluripotent Stem Cell (iPSC)-neuronal model is available yet to achieve mechanistic insights on cognitive impairment of RSTS patients. We established iPSC-derived neurons (i-neurons) from peripheral blood cells of three CREBBP- and two EP300-mutated patients displaying different levels of intellectual disability, and four unaffected controls. Pan neuronal and cortical-specific markers were expressed by all patients' i-neurons. Altered morphology of patients' differentiating neurons, showing reduced branch length and increased branch number, and hypoexcitability of differentiated neurons emerged as potential disease biomarkers. Anomalous neuronal morphology and reduced excitability varied across different RSTS patients' i-neurons. Further studies are needed to validate these markers and assess whether they reflect cognitive and behavioural impairment of the donor patients.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Rubinstein-Taybi
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Proteína de Ligação a CREB
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Proteína p300 Associada a E1A
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Adult
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
Stem Cell Res
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Itália