Amplification of human interneuron progenitors promotes brain tumors and neurological defects.
Science
; 375(6579): eabf5546, 2022 01 28.
Article
em En
| MEDLINE
| ID: mdl-35084981
ABSTRACT
Evolutionary development of the human brain is characterized by the expansion of various brain regions. Here, we show that developmental processes specific to humans are responsible for malformations of cortical development (MCDs), which result in developmental delay and epilepsy in children. We generated a human cerebral organoid model for tuberous sclerosis complex (TSC) and identified a specific neural stem cell type, caudal late interneuron progenitor (CLIP) cells. In TSC, CLIP cells over-proliferate, generating excessive interneurons, brain tumors, and cortical malformations. Epidermal growth factor receptor inhibition reduces tumor burden, identifying potential treatment options for TSC and related disorders. The identification of CLIP cells reveals the extended interneuron generation in the human brain as a vulnerability for disease. In addition, this work demonstrates that analyzing MCDs can reveal fundamental insights into human-specific aspects of brain development.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esclerose Tuberosa
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Encéfalo
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Neoplasias Encefálicas
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Células-Tronco Neurais
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Interneurônios
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Science
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Áustria