The destiny of the resistance/susceptibility against GCRV is controlled by epigenetic mechanisms in CIK cells.
The destiny of the resistance/susceptibility against GCRV is controlled by epigenetic mechanisms in CIK cells.
复制标题
CIK 细胞的表观遗传机制控制着 GCRV 的耐药性/易感性的命运
DOI：
10.1038/s41598-017-03990-5
复制
发表时间：
2017-07-03
影响因子：
4.6
通讯作者：
Su J
中科院分区：
文献类型：
--
作者：
Shang X;Yang C;Wan Q;Rao Y;Su J
由草鱼呼肠孤病毒（GCRV）引起的出血病严重威胁着草鱼（Ctenopharyngodon idella）养殖业。值得注意的是，已有报道称草鱼对GCRV感染的抗性具有遗传性，且在个体和细胞水平均得到了验证。因此，本研究受此启发，致力于揭示相关免疫细胞在感染GCRV后命运决定的分子机制。首先，通过单细胞分选、传代培养和感染筛选，相继建立了抗性和敏感的CIK（草鱼肾脏）单克隆细胞系。对C1（CIK细胞）、R2（抗性细胞）和S3（敏感细胞）组进行了RNA测序、甲基化DNA免疫沉淀测序（MeDIP - Seq）和小RNA测序。结果表明，S3组的全基因组DNA甲基化、mRNA和微小RNA表达水平在三组中最高。转录组分析表明，与抗氧化活性、细胞增殖调控、凋亡活性和能量消耗相关的通路可能有助于决定感染后细胞的命运。此外，还鉴定出一系列在抗性和敏感组间差异表达的免疫相关基因，这些基因受到DNA甲基化或微小RNA的负调控。综上所述，本研究从表观遗传学角度系统揭示了抗性的调控机制，为未来抗性育种研究提供了潜在的生物标志物。
Hemorrhagic disease caused by grass carp reovirus (GCRV) has severely threatened the grass carp (Ctenopharyngodon idella) cultivation industry. It is noteworthy that the resistance against GCRV infection was reported to be inheritable, and identified at both individual and cellular levels. Therefore, this work was inspired and dedicated to unravel the molecular mechanisms of fate decision post GCRV infection in related immune cells. Foremost, the resistant and susceptible CIK (C. idellakidney) monoclonal cells were established by single cell sorting, subculturing and infection screening successively. RNA-Seq, MeDIP-Seq and small RNA-Seq were carried out with C1 (CIK cells), R2 (resistant cells) and S3 (susceptible cells) groups. It was demonstrated that genome-wide DNA methylation, mRNA and microRNA expression levels in S3 were the highest among three groups. Transcriptome analysis elucidated that pathways associated with antioxidant activity, cell proliferation regulation, apoptosis activity and energy consuming might contribute to the decision of cell fates post infection. And a series of immune-related genes were identified differentially expressed across resistant and susceptible groups, which were negatively modulated by DNA methylation or microRNAs. To conclude, this study systematically uncovered the regulatory mechanism on the resistance from epigenetic perspective and provided potential biomarkers for future studies on resistance breeding.