Maternal immune activation in mice disrupts proteostasis in the fetal brain.
Maternal immune activation in mice disrupts proteostasis in the fetal brain.
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DOI：
10.1038/s41593-020-00762-9
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发表时间：
2021-03
影响因子：
25
通讯作者：
Huh JR
中科院分区：
文献类型：
--
作者：
Kalish BT;Kim E;Finander B;Duffy EE;Kim H;Gilman CK;Yim YS;Tong L;Kaufman RJ;Griffith EC;Choi GB;Greenberg ME;Huh JR
妊娠期间的母体感染和炎症与后代的神经发育障碍有关，但对这一流行病学现象背后的分子机制知之甚少。我们利用单细胞RNA测序来分析小鼠胎儿脑对母体免疫激活（MIA）的转录变化，并确定了与mRNA翻译、核糖体生物发生和应激信号相关的细胞通路的扰动。我们发现MIA以依赖白细胞介素-17a的方式激活雄性（而非雌性）MIA后代的综合应激反应（ISR），从而减少全球mRNA翻译并改变新生蛋白质组合成。此外，阻断ISR激活可以防止MIA雄性后代的行为异常和皮质神经活动的增加。我们的数据表明，ISR的性别特异性激活导致母体炎症相关的神经发育障碍。
Maternal infection and inflammation during pregnancy are associated with neurodevelopmental disorders in offspring, but little is understood about the molecular mechanisms underlying this epidemiologic phenomenon. We leveraged single-cell RNA sequencing to profile transcriptional changes in the mouse fetal brain in response to maternal immune activation (MIA) and identified perturbations in cellular pathways associated with mRNA translation, ribosome biogenesis, and stress signaling. We found that MIA activates the integrated stress response (ISR) in male, but not female, MIA offspring in an Interleukin-17a dependent manner, thereby reducing global mRNA translation and altering nascent proteome synthesis. Moreover, blockade of ISR activation prevented the behavioral abnormalities as well as an increase in cortical neural activity in MIA male offspring. Our data suggest that sex-specific activation of the ISR leads to maternal inflammation-associated neurodevelopmental disorders.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
64.8
作者：
Kim S;Kim H;Yim YS;Ha S;Atarashi K;Tan TG;Longman RS;Honda K;Littman DR;Choi GB;Huh JR
通讯作者：
Huh JR
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
16
作者：
Guan BJ;van Hoef V;Jobava R;Elroy-Stein O;Valasek LS;Cargnello M;Gao XH;Krokowski D;Merrick WC;Kimball SR;Komar AA;Koromilas AE;Wynshaw-Boris A;Topisirovic I;Larsson O;Hatzoglou M
通讯作者：
Hatzoglou M
影响因子：
25
作者：
Hrvatin S;Hochbaum DR;Nagy MA;Cicconet M;Robertson K;Cheadle L;Zilionis R;Ratner A;Borges-Monroy R;Klein AM;Sabatini BL;Greenberg ME
通讯作者：
Greenberg ME