Vermeersch Elien, Nuyttens Benedicte P, Tersteeg Claudia, Broos Katleen, De Meyer Simon F, Vanhoorelbeke Karen, Deckmyn Hans
Laboratory for Thrombosis Research, KU Leuven Campus Kulak, Kortrijk, Belgium.
TH Open. 2018 Sep 10;2(3):e272-e279. doi: 10.1055/s-0038-1670630. eCollection 2018 Jul.
Despite the absence of the genome in platelets, transcription profiling provides important insights into platelet function and can help clarify abnormalities in platelet disorders. The Bloodomics Consortium performed whole-genome expression analysis comparing in vitro-differentiated megakaryocytes (MKs) with in vitro-differentiated erythroblasts and different blood cell types. This allowed the identification of genes with upregulated expression in MKs compared with all other cell lineages, among the receptors BAMBI, LRRC32, ESAM, and DCBLD2. In a later correlative analysis of genome-wide platelet RNA expression with interindividual human platelet reactivity, LLRFIP and COMMD7 were additionally identified. A functional genomics approach using morpholino-based silencing in zebrafish identified various roles for all of these selected genes in thrombus formation. In this review, we summarize the role of the six identified genes in zebrafish and discuss how they correlate with subsequently performed mouse experiments.
尽管血小板中不存在基因组，但转录谱分析为血小板功能提供了重要见解，并有助于阐明血小板疾病中的异常情况。血液组学联盟进行了全基因组表达分析，将体外分化的巨核细胞（MKs）与体外分化的成红细胞及不同血细胞类型进行比较。这使得能够鉴定出与所有其他细胞谱系相比，在MKs中表达上调的基因，其中包括受体BAMBI、LRRC32、ESAM和DCBLD2。在随后一项关于全基因组血小板RNA表达与个体间人类血小板反应性的相关性分析中，还鉴定出了LLRFIP和COMMD7。一种利用基于吗啉代的斑马鱼基因沉默技术的功能基因组学方法，确定了所有这些选定基因在血栓形成中的各种作用。在这篇综述中，我们总结了斑马鱼中六个已鉴定基因的作用，并讨论它们与随后进行的小鼠实验的相关性。
