RRC ID 50070
Author Thion MS, Low D, Silvin A, Chen J, Grisel P, Schulte-Schrepping J, Blecher R, Ulas T, Squarzoni P, Hoeffel G, Coulpier F, Siopi E, David FS, Scholz C, Shihui F, Lum J, Amoyo AA, Larbi A, Poidinger M, Buttgereit A, Lledo PM, Greter M, Chan JKY, Amit I, Beyer M, Schultze JL, Schlitzer A, Pettersson S, Ginhoux F, Garel S.
Title Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner.
Journal Cell
Abstract Microglia are embryonically seeded macrophages that contribute to brain development, homeostasis, and pathologies. It is thus essential to decipher how microglial properties are temporally regulated by intrinsic and extrinsic factors, such as sexual identity and the microbiome. Here, we found that microglia undergo differentiation phases, discernable by transcriptomic signatures and chromatin accessibility landscapes, which can diverge in adult males and females. Remarkably, the absence of microbiome in germ-free mice had a time and sexually dimorphic impact both prenatally and postnatally: microglia were more profoundly perturbed in male embryos and female adults. Antibiotic treatment of adult mice triggered sexually biased microglial responses revealing both acute and long-term effects of microbiota depletion. Finally, human fetal microglia exhibited significant overlap with the murine transcriptomic signature. Our study shows that microglia respond to environmental challenges in a sex- and time-dependent manner from prenatal stages, with major implications for our understanding of microglial contributions to health and disease.
Volume 172(3)
Pages 500-516.e16
Published 2018-1-25
DOI 10.1016/j.cell.2017.11.042
PII S0092-8674(17)31432-0
PMID 29275859
PMC PMC5786503
MeSH Animals Brain / cytology Brain / embryology Brain / metabolism Cell Differentiation Cells, Cultured Chromatin Assembly and Disassembly Female Germ-Free Life* Humans Male Mice Mice, Inbred C57BL Microbiota* Microglia / cytology* Microglia / metabolism Pregnancy Prenatal Exposure Delayed Effects / microbiology* Sex Factors Transcriptome*
IF 38.637
Times Cited 164
Mice RBRC02704