Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner

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 m...

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Main Authors: Thion, Morgane Sonia, Low, Donovan, Silvin, Aymeric, Chen, Jinmiao, Grisel, Pauline, Schulte-Schrepping, Jonas, Blecher, Ronnie, Ulas, Thomas, Squarzoni, Paola, Hoeffel, Guillaume, Coulpier, Fanny, Siopi, Eleni, David, Friederike Sophie, Scholz, Claus, Foo, Shihui, Lum, Josephine, Amoyo, Arlaine Anne, Larbi, Anis, Poidinger, Michael, Buttgereit, Anne, Lledo, Pierre-Marie, Greter, Melanie, Chan, Jerry Kok Yen, Amit, Ido, Beyer, Marc, Schultze, Joachim Ludwig, Schlitzer, Andreas, Pettersson, Sven, Ginhoux, Florent, Garel, Sonia
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Journal Article
Language:English
Published: 2018
Subjects:
Online Access:https://hdl.handle.net/10356/87431
http://hdl.handle.net/10220/44422
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author Thion, Morgane Sonia
Low, Donovan
Silvin, Aymeric
Chen, Jinmiao
Grisel, Pauline
Schulte-Schrepping, Jonas
Blecher, Ronnie
Ulas, Thomas
Squarzoni, Paola
Hoeffel, Guillaume
Coulpier, Fanny
Siopi, Eleni
David, Friederike Sophie
Scholz, Claus
Foo, Shihui
Lum, Josephine
Amoyo, Arlaine Anne
Larbi, Anis
Poidinger, Michael
Buttgereit, Anne
Lledo, Pierre-Marie
Greter, Melanie
Chan, Jerry Kok Yen
Amit, Ido
Beyer, Marc
Schultze, Joachim Ludwig
Schlitzer, Andreas
Pettersson, Sven
Ginhoux, Florent
Garel, Sonia
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Thion, Morgane Sonia
Low, Donovan
Silvin, Aymeric
Chen, Jinmiao
Grisel, Pauline
Schulte-Schrepping, Jonas
Blecher, Ronnie
Ulas, Thomas
Squarzoni, Paola
Hoeffel, Guillaume
Coulpier, Fanny
Siopi, Eleni
David, Friederike Sophie
Scholz, Claus
Foo, Shihui
Lum, Josephine
Amoyo, Arlaine Anne
Larbi, Anis
Poidinger, Michael
Buttgereit, Anne
Lledo, Pierre-Marie
Greter, Melanie
Chan, Jerry Kok Yen
Amit, Ido
Beyer, Marc
Schultze, Joachim Ludwig
Schlitzer, Andreas
Pettersson, Sven
Ginhoux, Florent
Garel, Sonia
author_sort Thion, Morgane Sonia
collection NTU
description 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.
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spelling ntu-10356/874312020-11-01T05:18:48Z Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner Thion, Morgane Sonia Low, Donovan Silvin, Aymeric Chen, Jinmiao Grisel, Pauline Schulte-Schrepping, Jonas Blecher, Ronnie Ulas, Thomas Squarzoni, Paola Hoeffel, Guillaume Coulpier, Fanny Siopi, Eleni David, Friederike Sophie Scholz, Claus Foo, Shihui Lum, Josephine Amoyo, Arlaine Anne Larbi, Anis Poidinger, Michael Buttgereit, Anne Lledo, Pierre-Marie Greter, Melanie Chan, Jerry Kok Yen Amit, Ido Beyer, Marc Schultze, Joachim Ludwig Schlitzer, Andreas Pettersson, Sven Ginhoux, Florent Garel, Sonia Lee Kong Chian School of Medicine (LKCMedicine) School of Biological Sciences CXCR4 Antibiotics 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. Published version 2018-02-09T03:06:30Z 2019-12-06T16:41:45Z 2018-02-09T03:06:30Z 2019-12-06T16:41:45Z 2017 Journal Article Thion, M. S., Low, D., Silvin, A., Chen, J., Grisel, P., Schulte-Schrepping, J., et al. (2018). Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner. Cell, 172(3), 500-516. 0092-8674 https://hdl.handle.net/10356/87431 http://hdl.handle.net/10220/44422 10.1016/j.cell.2017.11.042 en Cell © 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). 34 p. application/pdf
spellingShingle CXCR4
Antibiotics
Thion, Morgane Sonia
Low, Donovan
Silvin, Aymeric
Chen, Jinmiao
Grisel, Pauline
Schulte-Schrepping, Jonas
Blecher, Ronnie
Ulas, Thomas
Squarzoni, Paola
Hoeffel, Guillaume
Coulpier, Fanny
Siopi, Eleni
David, Friederike Sophie
Scholz, Claus
Foo, Shihui
Lum, Josephine
Amoyo, Arlaine Anne
Larbi, Anis
Poidinger, Michael
Buttgereit, Anne
Lledo, Pierre-Marie
Greter, Melanie
Chan, Jerry Kok Yen
Amit, Ido
Beyer, Marc
Schultze, Joachim Ludwig
Schlitzer, Andreas
Pettersson, Sven
Ginhoux, Florent
Garel, Sonia
Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner
title Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner
title_full Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner
title_fullStr Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner
title_full_unstemmed Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner
title_short Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner
title_sort microbiome influences prenatal and adult microglia in a sex specific manner
topic CXCR4
Antibiotics
url https://hdl.handle.net/10356/87431
http://hdl.handle.net/10220/44422
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