Sex-Specific Effects of Testosterone on the Sexually Dimorphic Transcriptome and Epigenome of Embryonic Neural Stem/Progenitor Cells.
Sex-Specific Effects of Testosterone on the Sexually Dimorphic Transcriptome and Epigenome of Embryonic Neural Stem/Progenitor Cells.
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DOI：
10.1038/srep36916
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发表时间：
2016-11-15
影响因子：
4.6
通讯作者：
Vilain E
中科院分区：
文献类型：
--
作者：
Bramble MS;Roach L;Lipson A;Vashist N;Eskin A;Ngun T;Gosschalk JE;Klein S;Barseghyan H;Arboleda VA;Vilain E
哺乳动物大脑中性别差异产生的机制尚不清楚，但受到潜在遗传差异和性腺激素暴露的综合影响。利用小鼠胚胎神经干细胞（enc）模型来了解促进两性二态大脑发育的早期事件，我们发现了染色体性别和激素暴露之间的新相互作用，这些相互作用有助于早期大脑性别差异。rna测序鉴定出103个转录本在基线时在XX和XY eNSCs之间差异表达（FDR = 0.10）。用丙酸睾酮（TP）处理显示出性别特异性的基因表达变化，分别导致2854和792个转录本在XX和XY遗传背景下差异表达。在TP应答转录本中，作为影响组蛋白修饰和DNA甲基化模式的表观遗传调节因子的基因富集。我们观察到，TP在两性中引起5-甲基胞嘧啶丰度的整体下降，这种传递效应在细胞后代中保持不变。此外，我们确定TP与组蛋白尾部乙酰化的残基特异性改变有关。这些发现强调了雄激素作用于发育性中枢神经系统细胞的未知成分，并有助于早期激素组织启动和维持的新作用机制。
The mechanisms by which sex differences in the mammalian brain arise are poorly understood, but are influenced by a combination of underlying genetic differences and gonadal hormone exposure. Using a mouse embryonic neural stem cell (eNSC) model to understand early events contributing to sexually dimorphic brain development, we identified novel interactions between chromosomal sex and hormonal exposure that are instrumental to early brain sex differences. RNA-sequencing identified 103 transcripts that were differentially expressed between XX and XY eNSCs at baseline (FDR = 0.10). Treatment with testosterone-propionate (TP) reveals sex-specific gene expression changes, causing 2854 and 792 transcripts to become differentially expressed on XX and XY genetic backgrounds respectively. Within the TP responsive transcripts, there was enrichment for genes which function as epigenetic regulators that affect both histone modifications and DNA methylation patterning. We observed that TP caused a global decrease in 5-methylcytosine abundance in both sexes, a transmissible effect that was maintained in cellular progeny. Additionally, we determined that TP was associated with residue-specific alterations in acetylation of histone tails. These findings highlight an unknown component of androgen action on cells within the developmental CNS, and contribute to a novel mechanism of action by which early hormonal organization is initiated and maintained.
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影响因子：
4.3
作者：
Lenz KM;Nugent BM;McCarthy MM
通讯作者：
McCarthy MM
影响因子：
3.5
作者：
Mathews GA;Fane BA;Conway GS;Brook CG;Hines M
通讯作者：
Hines M
影响因子：
2.7
作者：
Roselli CE;Liu M;Hurn PD
通讯作者：
Hurn PD
Dnmt1 和 Dnmt3a 维持 DNA 甲基化并调节成人前脑神经元的突触功能
影响因子：
25
作者：
Feng, Jian;Zhou, Yu;Campbell, Susan L.;Le, Thuc;Li, En;Sweatt, J. David;Silva, Alcino J.;Fan, Guoping
通讯作者：
Fan, Guoping
DOI：
10.1016/s0169-328x(03)00339-5
发表时间：
2003-10-21
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Dewing, P;Shi, T;Vilain, E
通讯作者：
Vilain, E