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Immunity ; 56(9): 2152-2171.e13, 2023 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-37582369

RESUMEN

Microglia phenotypes are highly regulated by the brain environment, but the transcriptional networks that specify the maturation of human microglia are poorly understood. Here, we characterized stage-specific transcriptomes and epigenetic landscapes of fetal and postnatal human microglia and acquired corresponding data in induced pluripotent stem cell (iPSC)-derived microglia, in cerebral organoids, and following engraftment into humanized mice. Parallel development of computational approaches that considered transcription factor (TF) co-occurrence and enhancer activity allowed prediction of shared and state-specific gene regulatory networks associated with fetal and postnatal microglia. Additionally, many features of the human fetal-to-postnatal transition were recapitulated in a time-dependent manner following the engraftment of iPSC cells into humanized mice. These data and accompanying computational approaches will facilitate further efforts to elucidate mechanisms by which human microglia acquire stage- and disease-specific phenotypes.


Asunto(s)
Células Madre Pluripotentes Inducidas , Microglía , Humanos , Ratones , Animales , Redes Reguladoras de Genes , Encéfalo , Regulación de la Expresión Génica
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