Journal
SCIENCE
Volume 353, Issue 6301, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aad8670
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Funding
- European Research Council [309788]
- Israeli Science Foundation [1782/11]
- European Commission Seventh Framework Programme (EC FP7) BLUEPRINT consortium
- Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine
- Minerva Stiftung research grant
- Israeli Ministry of Science, Technology and Space
- David and Fela Shapell Family Foundation
- National Human Genome Research Institute Center for Excellence in Genome Science [1P50HG006193]
- Alan and Laraine Fischer Career Development Chair
- Advanced European Research Council [232835]
- EC FP7 HEALTH-2011 program [279017]
- Agence Nationale de la Recherche [ANR BLAN07-1_205752, ANR-11-BSV3-026-01]
- Fondation pour la Recherche Medicale [DEq. 20071210559, DEq. 20110421320]
- InCA (French National Cancer Institute) [13-10/405/AB-LC-HS]
- European Molecular Biology Organization (EMBO) [ALT766-2014]
- EC FP7 (Marie Curie Actions) [GA-2012-600394]
- European Research Council (ERC) [232835] Funding Source: European Research Council (ERC)
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Microglia, the resident myeloid cells of the central nervous system, play important roles in life-long brain maintenance and in pathology. Despite their importance, their regulatory dynamics during brain development have not been fully elucidated. Using genome-wide chromatin and expression profiling coupled with single-cell transcriptomic analysis throughout development, we found that microglia undergo three temporal stages of development in synchrony with the brain-early, pre-, and adult microglia-which are under distinct regulatory circuits. Knockout of the gene encoding the adult microglia transcription factor MAFB and environmental perturbations, such as those affecting the microbiome or prenatal immune activation, led to disruption of developmental genes and immune response pathways. Together, our work identifies a stepwise microglia developmental program integrating immune response pathways that may be associated with several neurodevelopmental disorders.
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