1 Department of Neurology, School of Medicine, University of California at Davis, Sacramento, CA, USA.
2 Department of Medicine, University of Alberta, Edmonton, Canada.
J Cereb Blood Flow Metab. 2019 Sep;39(9):1818-1835. doi: 10.1177/0271678X18769513. Epub 2018 Apr 13.
Understanding how the blood transcriptome of human intracerebral hemorrhage (ICH) differs from ischemic stroke (IS) and matched controls (CTRL) will improve understanding of immune and coagulation pathways in both disorders. This study examined RNA from 99 human whole-blood samples using GeneChip® HTA 2.0 arrays to assess differentially expressed transcripts of alternatively spliced genes between ICH, IS and CTRL. We used a mixed regression model with FDR-corrected (Dx) < 0.2 and < 0.005 and |FC| > 1.2 for individual comparisons. For time-dependent analyses, subjects were divided into four time-points: 0(CTRL), <24 h, 24-48 h, >48 h; 489 transcripts were differentially expressed between ICH and CTRL, and 63 between IS and CTRL. ICH had differentially expressed T-cell receptor and CD36 genes, and iNOS, TLR, macrophage, and T-helper pathways. IS had more non-coding RNA. ICH and IS both had angiogenesis, CTLA4 in T lymphocytes, CD28 in T helper cells, NFAT regulation of immune response, and glucocorticoid receptor signaling pathways. Self-organizing maps revealed 4357 transcripts changing expression over time in ICH, and 1136 in IS. Understanding ICH and IS transcriptomes will be useful for biomarker development, treatment and prevention strategies, and for evaluating how well animal models recapitulate human ICH and IS.
了解人类脑出血 (ICH) 的血液转录组与缺血性中风 (IS) 和匹配对照 (CTRL) 有何不同,将有助于我们更好地理解这两种疾病中的免疫和凝血途径。本研究使用 GeneChip® HTA 2.0 阵列检测了 99 个人全血样本的 RNA,以评估 ICH、IS 和 CTRL 之间差异表达的剪接基因的转录本。我们使用混合回归模型, FDR 校正 (Dx) < 0.2 和 < 0.005,以及个体比较的 |FC| > 1.2。对于时间依赖性分析,将受试者分为四个时间点:0(CTRL)、<24 h、24-48 h、>48 h;ICH 和 CTRL 之间有 489 个转录本差异表达,IS 和 CTRL 之间有 63 个转录本差异表达。ICH 有差异表达的 T 细胞受体和 CD36 基因,以及 iNOS、TLR、巨噬细胞和 T 辅助途径。IS 有更多的非编码 RNA。ICH 和 IS 都有血管生成、T 淋巴细胞中的 CTLA4、T 辅助细胞中的 CD28、NFAT 对免疫反应的调节以及糖皮质激素受体信号通路。自组织映射揭示了 ICH 中 4357 个转录本随时间变化表达,IS 中 1136 个转录本随时间变化表达。了解 ICH 和 IS 的转录组将有助于开发生物标志物、治疗和预防策略,并评估动物模型在多大程度上重现人类 ICH 和 IS。