Juzenas Simonas, Venkatesh Geetha, Hübenthal Matthias, Hoeppner Marc P, Du Zhipei Gracie, Paulsen Maren, Rosenstiel Philip, Senger Philipp, Hofmann-Apitius Martin, Keller Andreas, Kupcinskas Limas, Franke Andre, Hemmrich-Stanisak Georg
Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany.
Institute for Digestive Research, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas LT 44307, Lithuania.
Nucleic Acids Res. 2017 Sep 19;45(16):9290-9301. doi: 10.1093/nar/gkx706.
With this study, we provide a comprehensive reference dataset of detailed miRNA expression profiles from seven types of human peripheral blood cells (NK cells, B lymphocytes, cytotoxic T lymphocytes, T helper cells, monocytes, neutrophils and erythrocytes), serum, exosomes and whole blood. The peripheral blood cells from buffy coats were typed and sorted using FACS/MACS. The overall dataset was generated from 450 small RNA libraries using high-throughput sequencing. By employing a comprehensive bioinformatics and statistical analysis, we show that 3' trimming modifications as well as composition of 3' added non-templated nucleotides are distributed in a lineage-specific manner-the closer the hematopoietic progenitors are, the higher their similarities in sequence variation of the 3' end. Furthermore, we define the blood cell-specific miRNA and isomiR expression patterns and identify novel cell type specific miRNA candidates. The study provides the most comprehensive contribution to date towards a complete miRNA catalogue of human peripheral blood, which can be used as a reference for future studies. The dataset has been deposited in GEO and also can be explored interactively following this link: http://134.245.63.235/ikmb-tools/bloodmiRs.
通过本研究,我们提供了一个全面的参考数据集,该数据集包含来自七种人类外周血细胞(自然杀伤细胞、B淋巴细胞、细胞毒性T淋巴细胞、辅助性T细胞、单核细胞、中性粒细胞和红细胞)、血清、外泌体和全血的详细miRNA表达谱。使用荧光激活细胞分选术/磁性激活细胞分选术对血沉棕黄层中的外周血细胞进行分型和分选。整个数据集由450个小RNA文库通过高通量测序生成。通过全面的生物信息学和统计分析,我们发现3'端修剪修饰以及3'端添加的非模板化核苷酸的组成以谱系特异性方式分布——造血祖细胞越接近,其3'端序列变异的相似性越高。此外,我们定义了血细胞特异性miRNA和异源miR表达模式,并鉴定了新的细胞类型特异性miRNA候选物。该研究为人类外周血完整的miRNA目录做出了迄今为止最全面的贡献,可作为未来研究的参考。该数据集已存入基因表达综合数据库(GEO),也可通过以下链接进行交互式探索:http://134.245.63.235/ikmb-tools/bloodmiRs。