Genomic modules and intramodular network concordance in susceptible and resilient male mice across models of stress.
Genomic modules and intramodular network concordance in susceptible and resilient male mice across models of stress.
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易感和弹性雄性小鼠在应激模型中的基因组模块和模内网络一致性。
DOI：
10.1038/s41386-021-01219-8
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Marrocco J
中科院分区：
文献类型：
--
作者：
Caradonna SG;Zhang TY;O'Toole N;Shen MJ;Khalil H;Einhorn NR;Wen X;Parent C;Lee FS;Akil H;Meaney MJ;McEwen BS;Marrocco J
应激相关疾病的多因素病因学需要不断询问临床前应激模型中的分子会聚，这些模型使用不同的范式作为应激源，从环境挑战到遗传易感性再到激素信号传导。使用RNA测序，我们研究了小鼠应激模型常见的腹侧海马体中的基因组特征。慢性口服皮质酮（CORT）诱导野生型雄性小鼠和脑源性神经营养因子Val 66 Met（一种与遗传易感性相关的应激变异体）基因编码杂合子雄性小鼠的焦虑和抑郁样行为增加。在另一组雄性小鼠中，慢性社会失败压力（CSDS）导致易感或弹性群体，其比例取决于住房条件，即标准住房或丰富的环境。秩-秩-超几何重叠（RRHO）是一种无阈值方法，通过基因的p值和效应大小方向对基因进行排序，用于从连续梯度的显著性中识别各组间一致的基因。在用CORT治疗的小鼠和标准饲养的易感小鼠中，差异表达基因（DEG）与参与神经传递、细胞骨架功能和血管形成的基因网络一致。加权基因共表达分析产生了54个基因枢纽模块，并揭示了两个模块，其中CORT和CSDS诱导富集DEG，其功能与RRHO预测一致，并与行为弹性或易感性相关。这些数据显示了跨模型的转录一致性，其中压力应对取决于激素，环境或遗传因素，揭示了体现压力相关疾病多方面性质的共同基因组驱动因素。
The multifactorial etiology of stress-related disorders necessitates a constant interrogation of the molecular convergences in preclinical models of stress that use disparate paradigms as stressors spanning from environmental challenges to genetic predisposition to hormonal signaling. Using RNA-sequencing, we investigated the genomic signatures in the ventral hippocampus common to mouse models of stress. Chronic oral corticosterone (CORT) induced increased anxiety- and depression-like behavior in wild-type male mice and male mice heterozygous for the gene coding for brain-derived neurotrophic factor Val66Met, a variant associated with genetic susceptibility to stress. In a separate set of male mice, chronic social defeat stress (CSDS) led to a susceptible or a resilient population, whose proportion was dependent on housing conditions, namely standard housing or enriched environment. Rank-rank-hypergeometric overlap (RRHO), a threshold-free approach that ranks genes by their p value and effect size direction, was used to identify genes from a continuous gradient of significancy that were concordant across groups. In mice treated with CORT and in standard-housed susceptible mice, differentially expressed genes (DEGs) were concordant for gene networks involved in neurotransmission, cytoskeleton function, and vascularization. Weighted gene co-expression analysis generated 54 gene hub modules and revealed two modules in which both CORT and CSDS-induced enrichment in DEGs, whose function was concordant with the RRHO predictions, and correlated with behavioral resilience or susceptibility. These data showed transcriptional concordance across models in which the stress coping depends upon hormonal, environmental, or genetic factors revealing common genomic drivers that embody the multifaceted nature of stress-related disorders.
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影响因子：
4.7
作者：
Chandramohan, Yalini;Droste, Susanne K.;Reul, Johannes M. H. M.
通讯作者：
Reul, Johannes M. H. M.
影响因子：
16.2
作者：
Fanselow, Michael S.;Dong, Hong-Wei
通讯作者：
Dong, Hong-Wei
影响因子：
4.6
作者：
Cahill KM;Huo Z;Tseng GC;Logan RW;Seney ML
通讯作者：
Seney ML
超越模块和集线器：基因共表达网络研究复杂脑疾病的分子机制的潜力。
DOI：
10.1111/gbb.12106
发表时间：
2014-01
期刊：
Genes, brain, and behavior
影响因子：
--
作者：
Gaiteri C;Ding Y;French B;Tseng GC;Sibille E
通讯作者：
Sibille E
影响因子：
6.1
作者：
Ardi, Ziv;Albrecht, Anne;Richter-Levin, Gal
通讯作者：
Richter-Levin, Gal