Human fetal microglia acquire homeostatic immune-sensing properties early in development

Microglia, immune cells of the central nervous system (CNS), are important for tissue development and maintenance, and are implicated in CNS disease, but we lack understanding of human fetal microglia development. Single-cell gene expression and bulk chromatin profiles of microglia at 9-18 gestational weeks (GWs) of human fetal development were generated. Microglia are heterogeneous at all studied GWs. Microglia start to mature during this developmental period and increasingly resemble adult microglia with CNS-surveilling properties. Chromatin accessibility increases during development with associated transcriptional networks reflective of adult microglia. Thus, during early fetal development, microglia progress towards a more mature, immune-sensing competent phenotype, which might render the developing human CNS vulnerable to environmental perturbations during early pregnancy