Profiling of Sexually Dimorphic Genes in Neural Cells to Identify Eif2s3y, Whose Overexpression Causes Autism-Like Behaviors in Male Mice.
Profiling of Sexually Dimorphic Genes in Neural Cells to Identify Eif2s3y, Whose Overexpression Causes Autism-Like Behaviors in Male Mice.
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分析神经细胞中的性别二态性基因以识别 Eif2s3y，其过度表达会导致雄性小鼠出现自闭症样行为
DOI：
10.3389/fcell.2021.669798
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发表时间：
2021
影响因子：
5.5
通讯作者：
Zhang YW
中科院分区：
文献类型：
--
作者：
Zhang M;Zhou Y;Jiang Y;Lu Z;Xiao X;Ning J;Sun H;Zhang X;Luo H;Can D;Lu J;Xu H;Zhang YW
许多神经系统疾病表现出性别差异和性别特异性治疗反应。不幸的是，大量研究这些神经系统疾病的分子和细胞机制的研究使用了性别不确定的原代细胞培养物;这可能是不同研究之间相互矛盾的结果的来源，并损害了研究结论的有效性。在此，我们全面比较了来自新生小鼠脑的原代神经元、星形胶质细胞和小胶质细胞中基因表达的性别二态性。我们发现，在这些原代细胞中，总体性二态基因数量相对较低，小胶质细胞拥有最多（264个基因），神经元拥有中等（69个基因），星形胶质细胞拥有最少（30个基因）。KEGG分析表明，这三种细胞类型中的性二态基因强烈富集免疫系统和免疫相关疾病。此外，我们确定了这些初级细胞所共有的性二型基因主要位于Y染色体上，包括Ddx 3 y，Eif 2s 3 y，Kdm 5d和Uty。最后，我们证明了Eif 2s 3 y的过度表达增加了雄性神经元的突触传递，并导致了雄性小鼠的自闭症样行为。总之，我们的研究结果表明，当这些细胞被用于研究神经系统疾病的性别偏见的易感性，特别是那些与免疫功能障碍相关的分子机制时，应考虑原代细胞的性别。此外，我们的研究结果表明，Y染色体上性二态基因的失调也可能导致自闭症和其他神经系统疾病，为神经系统疾病中性别差异的遗传驱动因素提供了新的见解。
Many neurological disorders exhibit sex differences and sex-specific therapeutic responses. Unfortunately, significant amounts of studies investigating molecular and cellular mechanisms underlying these neurological disorders use primary cell cultures with undetermined sexes; and this may be a source for contradictory results among different studies and impair the validity of study conclusion. Herein, we comprehensively compared sexual dimorphism of gene expression in primary neurons, astrocytes, and microglia derived from neonatal mouse brains. We found that overall sexually dimorphic gene numbers were relatively low in these primary cells, with microglia possessing the most (264 genes), neurons possessing the medium (69 genes), and astrocytes possessing the least (30 genes). KEGG analysis indicated that sexually dimorphic genes in these three cell types were strongly enriched for the immune system and immune-related diseases. Furthermore, we identified that sexually dimorphic genes shared by these primary cells dominantly located on the Y chromosome, including Ddx3y, Eif2s3y, Kdm5d, and Uty. Finally, we demonstrated that overexpression of Eif2s3y increased synaptic transmission specifically in male neurons and caused autism-like behaviors specifically in male mice. Together, our results demonstrate that the sex of primary cells should be considered when these cells are used for studying the molecular mechanism underlying neurological disorders with sex-biased susceptibility, especially those related to immune dysfunction. Moreover, our findings indicate that dysregulation of sexually dimorphic genes on the Y chromosome may also result in autism and possibly other neurological disorders, providing new insights into the genetic driver of sex differences in neurological disorders.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
自闭症谱系障碍与49，Xyyyy：案例报告和文献综述。
影响因子：
--
作者：
Demily C;Poisson A;Peyroux E;Gatellier V;Nicolas A;Rigard C;Schluth-Bolard C;Sanlaville D;Rossi M
通讯作者：
Rossi M
DOI：
10.1523/jneurosci.1268-12.2013
发表时间：
2013-02-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Lenz KM;Nugent BM;Haliyur R;McCarthy MM
通讯作者：
McCarthy MM
影响因子：
8.8
作者：
Guneykaya, Dilansu;Ivanov, Andranik;Wolf, Susanne A.
通讯作者：
Wolf, Susanne A.
影响因子：
10.6
作者：
Fung LK;Reiss AL
通讯作者：
Reiss AL