Human prefrontal cortex gene regulatory dynamics from gestation to adulthood at single-cell resolution.
Cell
; 185(23): 4428-4447.e28, 2022 11 10.
Article
en En
| MEDLINE
| ID: mdl-36318921
ABSTRACT
Human brain development is underpinned by cellular and molecular reconfigurations continuing into the third decade of life. To reveal cell dynamics orchestrating neural maturation, we profiled human prefrontal cortex gene expression and chromatin accessibility at single-cell resolution from gestation to adulthood. Integrative analyses define the dynamic trajectories of each cell type, revealing major gene expression reconfiguration at the prenatal-to-postnatal transition in all cell types followed by continuous reconfiguration into adulthood and identifying regulatory networks guiding cellular developmental programs, states, and functions. We uncover links between expression dynamics and developmental milestones, characterize the diverse timing of when cells acquire adult-like states, and identify molecular convergence from distinct developmental origins. We further reveal cellular dynamics and their regulators implicated in neurological disorders. Finally, using this reference, we benchmark cell identities and maturation states in organoid models. Together, this captures the dynamic regulatory landscape of human cortical development.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Organoides
/
Neurogénesis
Límite:
Adult
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Female
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Humans
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Pregnancy
Idioma:
En
Revista:
Cell
Año:
2022
Tipo del documento:
Article