Human microglia maturation is underpinned by specific gene regulatory networks

Birth Defects Research Laboratory, Claudia Z. Han

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2152-2171.e13
JournalImmunity
Volume56
Issue number9
DOIs
StatePublished - Sep 12 2023

Keywords

  • epigenomics
  • humanized
  • microglia
  • neurodevelopment
  • neurological disorders
  • stem cells
  • transcription factors
  • transcriptomics

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