Chromatin and gene-regulatory dynamics of the developing human cerebral cortex at single-cell resolution.
Cell
; 184(19): 5053-5069.e23, 2021 09 16.
Article
en En
| MEDLINE
| ID: mdl-34390642
ABSTRACT
Genetic perturbations of cortical development can lead to neurodevelopmental disease, including autism spectrum disorder (ASD). To identify genomic regions crucial to corticogenesis, we mapped the activity of gene-regulatory elements generating a single-cell atlas of gene expression and chromatin accessibility both independently and jointly. This revealed waves of gene regulation by key transcription factors (TFs) across a nearly continuous differentiation trajectory, distinguished the expression programs of glial lineages, and identified lineage-determining TFs that exhibited strong correlation between linked gene-regulatory elements and expression levels. These highly connected genes adopted an active chromatin state in early differentiating cells, consistent with lineage commitment. Base-pair-resolution neural network models identified strong cell-type-specific enrichment of noncoding mutations predicted to be disruptive in a cohort of ASD individuals and identified frequently disrupted TF binding sites. This approach illustrates how cell-type-specific mapping can provide insights into the programs governing human development and disease.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Cromatina
/
Corteza Cerebral
/
Regulación del Desarrollo de la Expresión Génica
/
Análisis de la Célula Individual
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cell
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos