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源自严重联合免疫缺陷(SCID)小鼠和BALB/c小鼠的比较转录组分析:寄生虫生长发育异常的线索

Comparative Transcriptome Analyses of Derived From SCID Mice and BALB/c Mice: Clues to the Abnormality in Parasite Growth and Development.

作者信息

Liu Rong, Cheng Wen-Jun, Ye Feng, Zhang Yao-Dan, Zhong Qin-Ping, Dong Hui-Fen, Tang Hong-Bin, Jiang Hong

机构信息

School of Basic Medical Sciences, Wuhan University, Wuhan, China.

Laboratory Animal Center, School of Medicine, Wuhan University, Wuhan, China.

出版信息

Front Microbiol. 2020 Mar 11;11:274. doi: 10.3389/fmicb.2020.00274. eCollection 2020.

DOI:10.3389/fmicb.2020.00274
PMID:32218772
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7078119/
Abstract

Schistosomiasis, caused by the parasitic flatworms called schistosomes, remains one of the most prevailing parasitic diseases in the world. The prodigious oviposition of female worms after maturity is the main driver of pathology due to infection, yet our understanding about the regulation of development and reproduction of schistosomes is limited. Here, we comparatively profiled the transcriptome of recovered from SCID and BALB/c mice, which were collected 35 days post-infection, when prominent morphological abnormalities could be observed in schistosomes from SCID mice, by performing RNA-seq analysis. Of the 11,183 identified genes, 62 differentially expressed genes (DEGs) with 39 upregulated and 23 downregulated messenger RNAs (mRNAs) were found in male worms from SCID mice (S_M) . male worms from BALB/c mice (B_M), and 240 DEGs with 152 upregulated and 88 downregulated mRNAs were found in female worms from SCID mice (S_F) . female worms from BALB/c mice (B_F). We also tested nine DEGs with a relatively higher expression abundance in the gonads of the worms (ovary, vitellaria, or testis), suggesting their potential biological significance in the development and reproduction of the parasites. Gene ontology (GO) enrichment analysis revealed that GO terms such as "microtubule-based process," "multicellular organismal development," and "Rho protein signal transduction" were significantly enriched in the DEGs in S_F . B_F, whereas GO terms such as "oxidation-reduction process," "response to stress," and "response to DNA damage stimulus" were significantly enriched in the DEGs in S_M . B_M. These results revealed that the differential expression of some important genes might contribute to the morphological abnormalities of worms in SCID mice. Furthermore, we selected one DEG, the mitochondrial prohibitin complex protein 1 (), to perform double-stranded RNA (dsRNA)-mediated RNA interference (RNAi) targeting the worms in BALB/c mice, and we found that it was essential for the growth and reproductive development of both male and female worms. Taken together, these results provided a wealth of information on the differential gene expression profiles of schistosomes from SCID mice when compared with those from BALB/c mice, which were potentially involved in regulating the growth and development of schistosomes. These findings contributed to an understanding of parasite biology and provided a rich resource for the exploitation of antischistosomal intervention targets.

摘要

血吸虫病由名为血吸虫的寄生扁虫引起,仍然是世界上最普遍的寄生虫病之一。成熟后雌虫大量产卵是感染所致病理变化的主要驱动因素,但我们对血吸虫发育和繁殖调控的了解有限。在此,我们通过RNA测序分析,比较了感染35天后从SCID小鼠和BALB/c小鼠体内收集的血吸虫的转录组,此时可观察到SCID小鼠体内的血吸虫出现明显的形态异常。在鉴定出的11,183个基因中,在SCID小鼠的雄虫(S_M)、BALB/c小鼠的雄虫(B_M)中发现了62个差异表达基因(DEG),其中39个信使核糖核酸(mRNA)上调,23个下调;在SCID小鼠的雌虫(S_F)、BALB/c小鼠的雌虫(B_F)中发现了240个DEG,其中152个mRNA上调,88个下调。我们还检测了在虫体性腺(卵巢、卵黄腺或睾丸)中表达丰度相对较高的9个DEG,表明它们在寄生虫发育和繁殖中具有潜在的生物学意义。基因本体(GO)富集分析显示,“基于微管的过程”“多细胞生物体发育”和“Rho蛋白信号转导”等GO术语在S_F和B_F的DEG中显著富集,而“氧化还原过程”“应激反应”和“对DNA损伤刺激的反应”等GO术语在S_M和B_M的DEG中显著富集。这些结果表明,一些重要基因的差异表达可能导致SCID小鼠体内虫体的形态异常。此外,我们选择了一个DEG,即线粒体抑制素复合体蛋白1(),对BALB/c小鼠体内的虫体进行双链RNA(dsRNA)介导的RNA干扰(RNAi),发现它对雌雄虫体的生长和生殖发育至关重要。综上所述,这些结果提供了大量关于SCID小鼠与BALB/c小鼠血吸虫差异基因表达谱的信息,这些差异基因可能参与调控血吸虫的生长和发育。这些发现有助于理解寄生虫生物学,并为开发抗血吸虫干预靶点提供了丰富资源。

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