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...
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Format: | Journal Article |
Language: | English |
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2018
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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. |
first_indexed | 2024-10-01T04:40:09Z |
format | Journal Article |
id | ntu-10356/87431 |
institution | Nanyang Technological University |
language | English |
last_indexed | 2024-10-01T04:40:09Z |
publishDate | 2018 |
record_format | dspace |
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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