TY - JOUR
T1 - Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner
AU - Thion, Morgane Sonia
AU - Low, Donovan
AU - Silvin, Aymeric
AU - Chen, Jinmiao
AU - Grisel, Pauline
AU - Schulte-Schrepping, Jonas
AU - Blecher, Ronnie
AU - Ulas, Thomas
AU - Squarzoni, Paola
AU - Hoeffel, Guillaume
AU - Coulpier, Fanny
AU - Siopi, Eleni
AU - David, Friederike Sophie
AU - Scholz, Claus
AU - Shihui, Foo
AU - Lum, Josephine
AU - Amoyo, Arlaine Anne
AU - Larbi, Anis
AU - Poidinger, Michael
AU - Buttgereit, Anne
AU - Lledo, Pierre-Marie
AU - Greter, Melanie
AU - Chan, Jerry Kok Yen
AU - Amit, Ido
AU - Beyer, Marc
AU - Schultze, Joachim Ludwig
AU - Schlitzer, Andreas
AU - Pettersson, Sven
AU - Ginhoux, Florent
AU - Garel, Sonia
N1 - We are grateful to the Garel and Ginhoux lab for discussions and critical comments on the manuscript. We thank Lucy Robinson for editing the manuscript, Esther Klingler and Samuel Collombet for scientific discussions, the IBENS Imaging Facility (France BioImaging, supported by ANR-10-INBS-04, ANR-10-LABX-54 MEMO LIFE and ANR-11-IDEX-000-02 PSL∗ Reseach University, “Investments for the future”), the cytometry core facility of Institut Curie for cell sorting, the IBENS transcriptomic facility (by the France Génomique national infrastructure, funded as part of the “Investissements d’Avenir” program [contract ANR-10-INBS-09]). We are grateful to C. Auger, A. Delecourt, E. Touzalin, D. Valera and C. Le Moal for excellent technical assistance. This work was supported by grants from the LKC School of Medicine, SCELSE, MOE (Tier1 grant), NIMBLE grant NTU, NTU GUTME grant, Swedish Medical Council (VR to S.P.), the DFG (SFB704 to J.L.S., M.B., and T.U. and SCHL 2116/1-1 to A.S.), the Federal Ministry for Economic Affairs and Energy (BMWi Project FASTGENOMICS to J.L.S.), the European Union’s Horizon 2020 (733100-SYSCID to M.B., J.S.S., and J.L.S.), INSERM, CNRS, the ERC Consolidator (NImO 616080 to S.G.), and from the Merlion Program (to S.G and F.G.). M.B., A.S., and J.L.S. are members of the Excellence Cluster ImmunoSensation. F.G. and S.G. are EMBO YIP awardees.
PY - 2018/1/25
Y1 - 2018/1/25
N2 - 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. Microglia respond to environmental challenges, such as signals from the gut microbiome, in a sex- and time-dependent manner.
AB - 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. Microglia respond to environmental challenges, such as signals from the gut microbiome, in a sex- and time-dependent manner.
U2 - 10.1016/j.cell.2017.11.042
DO - 10.1016/j.cell.2017.11.042
M3 - مقالة
C2 - 29275859
SN - 0092-8674
VL - 172
SP - 500-516.e16
JO - Cell
JF - Cell
IS - 3
ER -