Transcriptome analysis reveals sexual disparities in gene expression in rat brain microvessels.
Transcriptome analysis reveals sexual disparities in gene expression in rat brain microvessels.
复制标题
转录组分析揭示大鼠脑微血管基因表达的性别差异。
DOI：
10.1177/0271678x21999553
复制
发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Busija DW
中科院分区：
文献类型：
--
作者：
Chandra PK;Cikic S;Baddoo MC;Rutkai I;Guidry JJ;Flemington EK;Katakam PV;Busija DW
性别是脑微血管(MVS)功能和脑血管和神经疾病易感性的重要决定因素，但其潜在机制尚不清楚。利用高通量RNA测序分析，我们检测了幼年、雄性和雌性大鼠脑MVS中的差异表达(DE)基因。对23,786个已鉴定基因的生物信息学分析表明，根据错误发现率标准(FDR；p <； )，298个(1.2%)基因被诊断为DE，其中119个(40%)基因在男性和179个女性(60%)中大量表达。核酸结合、酶调节因子和转录因子是DE基因的前三位，男性高于女性。糖基磷脂酰肌醇(GPI)的合成、GPI锚定蛋白的生物合成、类固醇和胆固醇的合成是男性MVS中显著丰富的三个典型途径。相反，呼吸链、核糖体和3‘-UTR介导的翻译调控是女性MVS的前三个丰富的典型途径。通过蛋白质组学分析和Western blotting验证MVS的不同基因功能。我们的新发现揭示了MVS在基因表达和典型通路上的主要性别差异，这些差异为研究脑血管和其他神经疾病性别依赖差异的潜在机制和后果提供了基础。
Sex is an important determinant of brain microvessels (MVs) function and susceptibility to cerebrovascular and neurological diseases, but underlying mechanisms are unclear. Using high throughput RNA sequencing analysis, we examined differentially expressed (DE) genes in brain MVs from young, male, and female rats. Bioinformatics analysis of the 23,786 identified genes indicates that 298 (1.2%) genes were DE using False Discovery Rate criteria (FDR; p < 0.05), of which 119 (40%) and 179 (60%) genes were abundantly expressed in male and female MVs, respectively. Nucleic acid binding, enzyme modulator, and transcription factor were the top three DE genes, which were more highly expressed in male than female MVs. Synthesis of glycosylphosphatidylinositol (GPI), biosynthesis of GPI-anchored proteins, steroid and cholesterol synthesis, were the top three significantly enriched canonical pathways in male MVs. In contrast, respiratory chain, ribosome, and 3 ´-UTR-mediated translational regulation were the top three enriched canonical pathways in female MVs. Different gene functions of MVs were validated by proteomic analysis and western blotting. Our novel findings reveal major sex disparities in gene expression and canonical pathways of MVs and these differences provide a foundation to study the underlying mechanisms and consequences of sex-dependent differences in cerebrovascular and other neurological diseases.