Research Article

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

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Science  31 Jul 2020:
Vol. 369, Issue 6503, pp. 530-537
DOI: 10.1126/science.aba5906

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The development of microglia

Microglia are the brain's immune cells, and they play important roles in health and neurodegenerative disease. Kracht et al. performed single-cell analysis of human microglial gene expression and chromatin accessibility and compared the results with those of other studies of human and mice microglial development. By using in situ validation, these data identify fetal microglial subsets that appear to be distinct from adult human microglia, suggesting functional differences between the developing and mature brain.

Science, this issue p. 530

Abstract

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 to 18 gestational weeks (GWs) of human fetal development were generated. Microglia were 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 toward a more mature, immune-sensing competent phenotype, and this might render the developing human CNS vulnerable to environmental perturbations during early pregnancy.

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