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

对源自SCID小鼠和BALB/c小鼠的日本血吸虫进行比较转录组分析:揭示寄生虫生长发育异常的线索

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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 Schistosoma japonicum 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) vs. 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) vs. 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 vs. 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 vs. 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 (Phb1), to perform double-stranded RNA (dsRNA)-mediated RNA interference (RNAi) in vivo 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 S. japonicum 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.

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