Single-cell RNA-seq analyses show that long non-coding RNAs are conspicuously expressed in Schistosoma mansoni gamete and tegument progenitor cell populations.

Single-cell RNA-seq analyses show that long non-coding RNAs are conspicuously expressed in Schistosoma mansoni gamete and tegument progenitor cell populations.
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DOI:
10.3389/fgene.2022.924877
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发表时间:
2022
影响因子:
3.7
通讯作者:
--
中科院分区:
生物学3区
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曼氏血吸虫是一种引起血吸虫病的扁虫,血吸虫病是一种被忽视的热带疾病,影响着全球超过2亿人。需要新的治疗靶点,只有一种药物可供治疗,而没有疫苗。长非编码RNA(LncRNAs)是一种长度超过200个核苷酸的转录本,具有较低的或没有蛋白质编码潜力。在其他生物体中,它们被证明与生殖、干细胞维持和耐药性有关,并且往往表现出组织特异性的表达模式。曼氏链霉菌表达数以千计的lncRNA基因;然而,该寄生虫中lncRNAs的细胞型表达模式仍未确定。在这里,我们重新分析了从曼氏血吸虫成虫获得的公开可用的单细胞RNA测序(scRNA-seq)数据,以确定成虫血吸虫细胞类型的lncRNAs特征。共检测到8023个LncRNAs,占总LncRNAs的79%。使用严格的统计标准对细胞中的lncRNAs表达谱进行分析,以确定细胞团的74个lncRNA基因标记。雄配子和被皮祖谱系簇包含大多数簇特异的lncRNA标记。我们还鉴定了特定神经簇的lncRNA标记。用整装原位杂交和双荧光原位杂交验证了16个lncRNA基因中的13个(81%)在雄性和雌性成虫组织中具有簇特异性表达,其中一个基因座使用了两种不同的lncRNA亚型的探针,显示了在睾丸和卵巢中的差异表达。在我们的分析中检测到的所有lncRNA的细胞团的表达谱图谱可作为公共网站资源(http://verjolab.usp.br:8081).本研究结果为曼氏血吸虫的组织特异性表达和lncRNAs的调控表达程序提供了强有力的支持。这将为进一步探索lncRNA基因作为潜在的治疗靶点奠定基础。
Schistosoma mansoni is a flatworm that causes schistosomiasis, a neglected tropical disease that affects over 200 million people worldwide. New therapeutic targets are needed with only one drug available for treatment and no vaccine. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with low or no protein-coding potential. In other organisms, they have been shown as involved with reproduction, stem cell maintenance and drug resistance, and they tend to exhibit tissue-specific expression patterns. S. mansoni expresses thousands of lncRNA genes; however, the cell type expression patterns of lncRNAs in the parasite remain uncharacterized. Here, we have re-analyzed publicly available single-cell RNA-sequencing (scRNA-seq) data obtained from adult S. mansoni to identify the lncRNAs signature of adult schistosome cell types. A total of 8023 lncRNAs (79% of all lncRNAs) were detected. Analyses of the lncRNAs expression profiles in the cells using statistically stringent criteria were performed to identify 74 lncRNA gene markers of cell clusters. Male gamete and tegument progenitor lineages clusters contained most of the cluster-specific lncRNA markers. We also identified lncRNA markers of specific neural clusters. Whole-mount in situ hybridization (WISH) and double fluorescence in situ hybridization were used to validate the cluster-specific expression of 13 out of 16 selected lncRNA genes (81%) in the male and female adult parasite tissues; for one of these 16 gene loci, probes for two different lncRNA isoforms were used, which showed differential isoform expression in testis and ovary. An atlas of the expression profiles across the cell clusters of all lncRNAs detected in our analysis is available as a public website resource (http://verjolab.usp.br:8081). The results presented here give strong support to a tissue-specific expression and to a regulated expression program of lncRNAs in S. mansoni. This will be the basis for further exploration of lncRNA genes as potential therapeutic targets.
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