A Single-Cell Roadmap of Lineage Bifurcation in Human ESC Models of Embryonic Brain Development.
Cell Stem Cell
; 20(1): 120-134, 2017 01 05.
Article
em En
| MEDLINE
| ID: mdl-28094016
ABSTRACT
During human brain development, multiple signaling pathways generate diverse cell types with varied regional identities. Here, we integrate single-cell RNA sequencing and clonal analyses to reveal lineage trees and molecular signals underlying early forebrain and mid/hindbrain cell differentiation from human embryonic stem cells (hESCs). Clustering single-cell transcriptomic data identified 41 distinct populations of progenitor, neuronal, and non-neural cells across our differentiation time course. Comparisons with primary mouse and human gene expression data demonstrated rostral and caudal progenitor and neuronal identities from early brain development. Bayesian analyses inferred a unified cell-type lineage tree that bifurcates between cortical and mid/hindbrain cell types. Two methods of clonal analyses confirmed these findings and further revealed the importance of Wnt/ß-catenin signaling in controlling this lineage decision. Together, these findings provide a rich transcriptome-based lineage map for studying human brain development and modeling developmental disorders.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Linhagem da Célula
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Desenvolvimento Embrionário
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Análise de Célula Única
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Células-Tronco Embrionárias Humanas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Cell Stem Cell
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos