Sex-based eRNA expression and function in ischemic stroke.
Sex-based eRNA expression and function in ischemic stroke.
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DOI：
10.1016/j.neuint.2021.105149
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发表时间：
2021-11
影响因子：
4.2
通讯作者：
Dharap A
中科院分区：
文献类型：
--
作者：
Ruiz D;Bhattarai S;Dharap A
增强子衍生的RNA（eRNA）是一类新的长链非编码RNA，其在调节增强子介导的基因转录中发挥作用，最终影响表型结果。我们最近发表了第一项研究，绘制了缺血性中风期间雄性小鼠皮质中全基因组eRNA表达，并确定了77种eRNA，与假手术对照组相比，大脑中动脉闭塞（MCAO）1小时和再灌注6小时后发生了显著变化。敲低一种这样的中风诱导的eRNA-eRNA_06347-导致显著更大的梗死，证明了eRNA_06347在调节男性中风后病理生理学中的作用。在目前的研究中，我们应用定量实时PCR来评估在男性皮质中鉴定的77种eRNA是否也在中风后女性皮质中显示出改变的表达。使用年龄匹配和时间匹配的雌性小鼠，我们发现在中风后的女性皮质中只检测到77种eRNA的一个子集。其中，只有一小部分显示出与雄性相似的时间表达特征，包括eRNA_06347，其在两种性别中均被高度诱导。雌性皮质中eRNA_06347的敲低导致梗死体积显著增加，这与雄性中的梗死体积密切匹配，表明eRNA_06347在雄性和雌性中类似地调节中风后病理生理学。这表明eRNA_06347在两性中具有共同的潜在作用。总的来说，这是第一项评估中风期间女性皮质中eRNA表达和扰动的研究，并对男性和女性进行了比较分析。我们的研究结果表明，eRNA具有性别依赖和性别无关的表达模式，可能是重要的病理生理反应，中风在两个性别。
Enhancer-derived RNAs (eRNAs) are a new class of long noncoding RNA that have roles in modulating enhancer-mediated gene transcription, which ultimately influences phenotypic outcomes. We recently published the first study mapping genome-wide eRNA expression in the male mouse cortex during ischemic stroke and identified 77 eRNAs that were significantly altered following a 1 h middle cerebral artery occlusion (MCAO) and 6 h of reperfusion, as compared to sham controls. Knockdown of one such stroke-induced eRNA - eRNA_06347 - resulted in significantly larger infarcts, demonstrating a role for eRNA_06347 in modulating the post-stroke pathophysiology in males. In the current study, we applied quantitative real-time PCR to evaluate whether the 77 eRNAs identified in the male cortex also show altered expression in the post-stroke female cortex. Using age-matched and time-matched female mice, we found that only a subset of the 77 eRNAs were detected in the post-stroke female cortex. Of these, only a small fraction showed similar temporal expression characteristics as males, including eRNA_06347 which was highly induced in both sexes. Knockdown of eRNA_06347 in the female cortex resulted in significantly increased infarct volumes that were closely matched to those in males, indicating that eRNA_06347 modulates the post-stroke pathophysiology similarly in males and females. This suggests a common underlying role for eRNA_06347 in the two sexes. Overall, this is the first study to evaluate eRNA expression and perturbation in the female cortex during stroke, and present a comparative analysis between males and females. Our findings show that eRNAs have sex-dependent and sex-independent expression patterns that may be of significance to the pathophysiological responses to stroke in the two sexes.
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影响因子：
5.1
作者：
Bhattarai S;Akella A;Gandhi A;Dharap A
通讯作者：
Dharap A
DOI：
10.1073/pnas.1324151111
发表时间：
2014-05-20
影响因子：
11.1
作者：
Hsieh, Chen-Lin;Fei, Teng;Kantoff, Philip W.
通讯作者：
Kantoff, Philip W.
影响因子：
16
作者：
Kaikkonen, Minna U.;Spann, Nathanael J.;Heinz, Sven;Romanoski, Casey E.;Allison, Karmel A.;Stender, Joshua D.;Chun, Hyun B.;Tough, David F.;Prinjha, Rab K.;Benner, Christopher;Glass, Christopher K.
通讯作者：
Glass, Christopher K.
DOI：
10.1126/science.1259418
发表时间：
2015-02-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Arner E;Daub CO;Vitting-Seerup K;Andersson R;Lilje B;Drabløs F;Lennartsson A;Rönnerblad M;Hrydziuszko O;Vitezic M;Freeman TC;Alhendi AM;Arner P;Axton R;Baillie JK;Beckhouse A;Bodega B;Briggs J;Brombacher F;Davis M;Detmar M;Ehrlund A;Endoh M;Eslami A;Fagiolini M;Fairbairn L;Faulkner GJ;Ferrai C;Fisher ME;Forrester L;Goldowitz D;Guler R;Ha T;Hara M;Herlyn M;Ikawa T;Kai C;Kawamoto H;Khachigian LM;Klinken SP;Kojima S;Koseki H;Klein S;Mejhert N;Miyaguchi K;Mizuno Y;Morimoto M;Morris KJ;Mummery C;Nakachi Y;Ogishima S;Okada-Hatakeyama M;Okazaki Y;Orlando V;Ovchinnikov D;Passier R;Patrikakis M;Pombo A;Qin XY;Roy S;Sato H;Savvi S;Saxena A;Schwegmann A;Sugiyama D;Swoboda R;Tanaka H;Tomoiu A;Winteringham LN;Wolvetang E;Yanagi-Mizuochi C;Yoneda M;Zabierowski S;Zhang P;Abugessaisa I;Bertin N;Diehl AD;Fukuda S;Furuno M;Harshbarger J;Hasegawa A;Hori F;Ishikawa-Kato S;Ishizu Y;Itoh M;Kawashima T;Kojima M;Kondo N;Lizio M;Meehan TF;Mungall CJ;Murata M;Nishiyori-Sueki H;Sahin S;Nagao-Sato S;Severin J;de Hoon MJ;Kawai J;Kasukawa T;Lassmann T;Suzuki H;Kawaji H;Summers KM;Wells C;FANTOM Consortium;Hume DA;Forrest AR;Sandelin A;Carninci P;Hayashizaki Y
通讯作者：
Hayashizaki Y
影响因子：
37.8
作者：
Mirtschink, Peter;Bischof, Corinne;Krishnan, Jaya
通讯作者：
Krishnan, Jaya