Characterization of the platelet transcriptome by RNA sequencing in patients with acute myocardial infarction.
Characterization of the platelet transcriptome by RNA sequencing in patients with acute myocardial infarction.
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DOI：
10.3109/09537104.2015.1083543
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发表时间：
2016
期刊：
影响因子：
3.3
通讯作者：
Johnson AD
中科院分区：
文献类型：
--
作者：
Eicher JD;Wakabayashi Y;Vitseva O;Esa N;Yang Y;Zhu J;Freedman JE;McManus DD;Johnson AD
血小板中的转录本主要由前体巨核细胞产生，但在血小板翻译RNA和调节蛋白质/RNA水平时保持生理活性。最近使用转录组测序(RNA-seq)的研究表征了数量有限的非疾病个体的血小板转录组。在这里，我们通过在32例急性心肌梗死(MI)患者的血小板中完成RNA-SEQ来扩展这些RNA-SEQ研究。我们的目标是利用一组急性心肌梗死患者来描述血小板转录组的特征，并将基因表达与血小板聚集指标和ST段抬高心肌梗死(STEMI)(n=16)与非STEMI(n=16)亚型相关。与其他研究类似，我们检测到9,565个表达转录本，包括几个已知的血小板富集型标记物(例如，PPBP、OST4)。我们的RNA-SEQ数据与独立确定的血小板表达数据密切相关，并显示了与血小板相关的途径(例如，创伤反应、止血和血小板激活)以及肌动蛋白相关和转录后过程的丰富。与NSTEMI相比，STEMI的几个转录本显示出高表达(FBXL4、ECHDC3、KCNE1、TAOK2、AURKB、ERG和FKBP5)和低表达(MIAT、PVRL3和PZP)。我们还鉴定了与血小板聚集相关的转录本：TRAP(ATP6V1G2，SLC2A3)、胶原(CEACAM1，ITGA2)和ADP(PDGFB，PDGFC，ST3GAL6)。我们的研究通过提供从急性心肌梗死患者分离的血小板的转录组范围的分析，增加了目前的血小板基因表达资源。结合以前的研究，我们确定了与血小板功能和急性心肌梗死有关的各种基因，以供进一步研究。未来对更多不同的健康和疾病样本进行的血小板RNA-SEQ研究将增加我们对血小板血栓形成和非血栓功能的了解。
Transcripts in platelets are largely produced in precursor megakaryocytes but remain physiologically-active as platelets translate RNAs and regulate protein/RNA levels. Recent studies using transcriptome sequencing (RNA-seq) characterized the platelet transcriptome in limited numbers of non-diseased individuals. Here, we expand upon these RNA-seq studies by completing RNA-seq in platelets from 32 patients with acute myocardial infarction (MI). Our goals were to characterize the platelet transcriptome using a population of patients with acute MI and relate gene expression to platelet aggregation measures and ST-segment elevation MI (STEMI) (n=16) versus non-STEMI (NSTEMI) (n=16) subtypes. Similar to other studies, we detected 9,565 expressed transcripts, including several known platelet-enriched markers (e.g., PPBP, OST4). Our RNA-seq data strongly correlated with independently ascertained platelet expression data and showed enrichment for platelet-related pathways (e.g., wound response, hemostasis, and platelet activation), as well as actin-related and post-transcriptional processes. Several transcripts displayed suggestively higher (FBXL4, ECHDC3, KCNE1, TAOK2, AURKB, ERG, and FKBP5) and lower (MIAT, PVRL3and PZP) expression in STEMI platelets compared to NSTEMI. We also identified transcripts correlated with platelet aggregation to TRAP (ATP6V1G2, SLC2A3), collagen (CEACAM1, ITGA2), and ADP (PDGFB, PDGFC, ST3GAL6). Our study adds to current platelet gene expression resources by providing transcriptome-wide analyses in platelets isolated from patients with acute MI. In concert with prior studies, we identify various genes for further study in regards to platelet function and acute MI. Future platelet RNA-seq studies examining more diverse sets of healthy and diseased samples will add to our understanding of platelet thrombotic and non-thrombotic functions.