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Microglia development follows a stepwise program to regulate brain homeostasis

Item Type:Article
Title:Microglia development follows a stepwise program to regulate brain homeostasis
Creators Name:Matcovitch-Natan, O. and Winter, D.R. and Giladi, A. and Vargas Aguilar, S. and Spinrad, A. and Sarrazin, S. and Ben-Yehuda, H. and David, E. and Zelada González, F. and Perrin, P. and Keren-Shaul, H. and Gury, M. and Lara-Astaiso, D. and Thaiss, C.A. and Cohen, M. and Bahar Halpern, K. and Baruch, K. and Deczkowska, A. and Lorenzo-Vivas, E. and Itzkovitz, S. and Elinav, E. and Sieweke, M.H. and Schwartz, M. and Amit, I.
Abstract:Microglia, the resident myeloid cells of the central nervous system, play important roles in life-long brain maintenance and in pathology. Despite their crucial role, their regulatory dynamics during brain development have not been fully elucidated. Genome-wide chromatin and expression profiling coupled with single-cell transcriptomic analysis throughout development reveal that microglia undergo three temporal developmental stages in synchrony with the brain: early, pre-, and adult microglia, which are under distinct regulatory circuits. Knockout of 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 developmental program of microglia integrating immune response pathways that may be associated with several neurodevelopmental disorders.
Keywords:Blood-Brain Barrier, Brain, Chromatin, Gene Expression Profiling, Gene Knockout Techniques, Genetic Epigenesis, Histone Code, Homeostasis, Immunity, MafB Transcription Factor, Microglia, Myeloid Cells, Neurogenesis, Single-Cell Analysis, Animals, Mice
Publisher:American Association for the Advancement of Science
Page Range:aad8670
Date:19 August 2016
Official Publication:https://doi.org/10.1126/science.aad8670
PubMed:View item in PubMed

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