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Science. 2016 Aug 19;353(6301):aad8670. doi: 10.1126/science.aad8670. Epub 2016 Jun 23.

Microglia development follows a stepwise program to regulate brain homeostasis.

Author information

1
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
2
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
3
Centre d'Immunologie de Marseille-Luminy (CIML), Université Aix-Marseille, UM2, Campus de Luminy, Marseille, France. Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, Marseille, France. Centre National de la Recherche Scientifique (CNRS), UMR7280, Marseille, France. Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft (MDC), Robert-Rössle-Straß 10, 13125 Berlin, Germany.
4
Centre d'Immunologie de Marseille-Luminy (CIML), Université Aix-Marseille, UM2, Campus de Luminy, Marseille, France. Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, Marseille, France. Centre National de la Recherche Scientifique (CNRS), UMR7280, Marseille, France.
5
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
6
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
7
Centre d'Immunologie de Marseille-Luminy (CIML), Université Aix-Marseille, UM2, Campus de Luminy, Marseille, France. Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, Marseille, France. Centre National de la Recherche Scientifique (CNRS), UMR7280, Marseille, France. Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft (MDC), Robert-Rössle-Straß 10, 13125 Berlin, Germany. sieweke@ciml.univ-mrs.fr michal.schwartz@weizmann.ac.il ido.amit@weizmann.ac.il.
8
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel. sieweke@ciml.univ-mrs.fr michal.schwartz@weizmann.ac.il ido.amit@weizmann.ac.il.
9
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. sieweke@ciml.univ-mrs.fr michal.schwartz@weizmann.ac.il ido.amit@weizmann.ac.il.

Abstract

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.

PMID:
27338705
DOI:
10.1126/science.aad8670
[Indexed for MEDLINE]
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