Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Cell Stem Cell ; 20(1): 120-134, 2017 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-28094016

RESUMO

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.


Assuntos
Encéfalo/embriologia , Linhagem da Célula , Desenvolvimento Embrionário , Células-Tronco Embrionárias Humanas/citologia , Análise de Célula Única/métodos , Animais , Encéfalo/metabolismo , Linhagem Celular , Linhagem da Célula/genética , Células Clonais , Desenvolvimento Embrionário/genética , Humanos , Camundongos , Modelos Biológicos , Neurônios/citologia , Neurônios/metabolismo , Reprodutibilidade dos Testes , Análise de Sequência de RNA , Fatores de Transcrição/metabolismo , Transcriptoma/genética , Via de Sinalização Wnt/genética
2.
Nature ; 535(7612): 367-75, 2016 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-27409810

RESUMO

The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high-resolution transcriptional atlas of rhesus monkey (Macaca mulatta) brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical division of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons. Cortical layers and areas acquire adult-like molecular profiles surprisingly late in postnatal development. Disparate cell populations exhibit distinct developmental timing of gene expression, but also unexpected synchrony of processes underlying neural circuit construction including cell projection and adhesion. Candidate risk genes for neurodevelopmental disorders including primary microcephaly, autism spectrum disorder, intellectual disability, and schizophrenia show disease-specific spatiotemporal enrichment within developing neocortex. Human developmental expression trajectories are more similar to monkey than rodent, although approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny compared to monkey.


Assuntos
Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Macaca mulatta/genética , Transcriptoma , Envelhecimento/genética , Animais , Transtorno do Espectro Autista/genética , Encéfalo/citologia , Encéfalo/embriologia , Adesão Celular , Sequência Conservada , Feminino , Humanos , Deficiência Intelectual/genética , Masculino , Microcefalia/genética , Neocórtex/embriologia , Neocórtex/crescimento & desenvolvimento , Neocórtex/metabolismo , Transtornos do Neurodesenvolvimento/genética , Neurogênese/genética , Fatores de Risco , Esquizofrenia/genética , Análise Espaço-Temporal , Especificidade da Espécie , Transcrição Gênica/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...