Modeling neural tube development by differentiation of human embryonic stem cells in a microfluidic WNT gradient.
Nat Biotechnol
; 38(11): 1265-1273, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-32451506
ABSTRACT
The study of brain development in humans is limited by the lack of tissue samples and suitable in vitro models. Here, we model early human neural tube development using human embryonic stem cells cultured in a microfluidic device. The approach, named microfluidic-controlled stem cell regionalization (MiSTR), exposes pluripotent stem cells to signaling gradients that mimic developmental patterning. Using a WNT-activating gradient, we generated a neural tissue exhibiting progressive caudalization from forebrain to midbrain to hindbrain, including formation of isthmic organizer characteristics. Single-cell transcriptomics revealed that rostro-caudal organization was already established at 24 h of differentiation, and that the first markers of a neural-specific transcription program emerged in the rostral cells at 48 h. The transcriptomic hallmarks of rostro-caudal organization recapitulated gene expression patterns of the early rostro-caudal neural plate in mouse embryos. Thus, MiSTR will facilitate research on the factors and processes underlying rostro-caudal neural tube patterning.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
/
Microfluídica
/
Proteínas Wnt
/
Tubo Neural
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Células-Tronco Embrionárias Humanas
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Nat Biotechnol
Assunto da revista:
BIOTECNOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Dinamarca