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Science ; 364(6440)2019 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-31073041

RESUMO

During corticogenesis, distinct subtypes of neurons are sequentially born from ventricular zone progenitors. How these cells are molecularly temporally patterned is poorly understood. We used single-cell RNA sequencing at high temporal resolution to trace the lineage of the molecular identities of successive generations of apical progenitors (APs) and their daughter neurons in mouse embryos. We identified a core set of evolutionarily conserved, temporally patterned genes that drive APs from internally driven to more exteroceptive states. We found that the Polycomb repressor complex 2 (PRC2) epigenetically regulates AP temporal progression. Embryonic age-dependent AP molecular states are transmitted to their progeny as successive ground states, onto which essentially conserved early postmitotic differentiation programs are applied, and are complemented by later-occurring environment-dependent signals. Thus, epigenetically regulated temporal molecular birthmarks present in progenitors act in their postmitotic progeny to seed adult neuronal diversity.


Assuntos
Neocórtex/embriologia , Células-Tronco Neoplásicas/citologia , Neurogênese/fisiologia , Neurônios/citologia , Animais , Epigênese Genética , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Neocórtex/citologia , Células-Tronco Neoplásicas/metabolismo , Neurogênese/genética , Neurônios/metabolismo , Complexo Repressor Polycomb 2/metabolismo , RNA Mensageiro/metabolismo , Análise de Sequência de RNA , Análise de Célula Única , Transcrição Gênica
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