Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner.
Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner.
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微生物组以性别特异性影响产前和成年小胶质细胞。
DOI：
10.1016/j.cell.2017.11.042
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发表时间：
2018-01-25
期刊：
影响因子：
64.5
通讯作者：
Garel S
中科院分区：
文献类型：
--
作者：
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
小胶质细胞是胚胎播种的巨噬细胞，有助于大脑发育、动态平衡和病理。因此，破译小胶质细胞的特性如何在时间上受到内在和外在因素的调节是至关重要的，例如性别认同和微生物组。在这里，我们发现小胶质细胞经历了分化阶段，可以通过转录特征和染色质可及性景观来区分，这在成年男性和女性中可能有所不同。值得注意的是，无菌小鼠中微生物组的缺失在出生前和出生后都产生了一段时间和性别二型性的影响：小胶质细胞在雄性胚胎和雌性成年鼠中受到了更深的干扰。成年小鼠的抗生素治疗引发了性偏见的小胶质细胞反应，揭示了微生物区系枯竭的急性和长期影响。最后，人类胎儿小胶质细胞表现出与小鼠转录特征的显著重叠。我们的研究表明，小胶质细胞从出生前就以性别和时间依赖的方式响应环境挑战，这对于我们理解小胶质细胞对健康和疾病的贡献具有重要意义。小胶质细胞在发育过程中经历一系列的分化阶段母体微生物组在产前阶段影响小胶质细胞的特性缺乏微生物组对小胶质细胞有性别和时间上的特定影响微生物组的枯竭对小胶质细胞特性有急性和长期的影响小胶质细胞以性别和时间依赖的方式响应环境挑战，如来自肠道微生物组的信号。
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 undergo sequential phases of differentiation during development The maternal microbiome influences microglial properties during prenatal stages The absence of the microbiome has a sex- and time-specific impact on microglia Microbiome depletions have acute and long-term effects on microglial properties Microglia respond to environmental challenges, such as signals from the gut microbiome, in a sex- and time-dependent manner.
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