Functional genomic characterization of germinal cells in larval Schistosoma mansoni

RNA-seq experiments to identify gene expression changes following miracidia to sporocyst transformation in Schistosoma mansoni. Schistosomes infect hundreds of millions of people in the developing world. Transmission of these parasites relies on a stem cell-driven, clonal expansion of larvae inside a molluscan intermediate host. How this novel asexual reproductive strategy relates to current models of stem cell maintenance and germline specification is unclear. Here, we demonstrate that this proliferative larval cell population (germinal cells) shares some molecular signatures with stem cells from diverse organisms, in particular neoblasts of planarians (free-living relatives of schistosomes). We identify two distinct germinal cell lineages that differ in their proliferation kinetics and expression of a nanos ortholog. We show that a vasa PL10 homolog is required for proliferation and maintenance of both populations; whereas, argonaute2 and a fibroblast growth factor receptor-encoding gene are required only for nanos-negative cells. Our results suggest that an ancient stem cell-based developmental program may have enabled the evolution of the complex life-cycle of parasitic flatworms. Overall design: Total RNA was purified from ~10,000 freshly hatched miracidia or sporocysts 48 h post-transformation.

本数据集为针对曼氏血吸虫（Schistosoma mansoni）毛蚴（miracidia）向胞蚴（sporocyst）转化过程中基因表达变化开展的RNA测序（RNA-seq）实验。血吸虫在发展中国家感染数亿人口，其传播依赖于软体动物中间宿主体内由干细胞驱动的幼虫克隆扩增。目前，这种新型无性繁殖策略与现有干细胞维持及生殖系特化模型之间的关联尚不明确。
本研究证实，该具有增殖活性的幼虫细胞群（生殖系细胞）与多种生物的干细胞共享部分分子特征，尤以血吸虫的自由生活近亲——涡虫的新胚细胞（neoblasts）为甚。研究团队鉴定出两种截然不同的生殖系细胞谱系，二者在增殖动力学及nanos同源基因的表达模式上存在显著差异。实验结果显示，vasa PL10同源基因对这两种细胞群的增殖与维持均不可或缺；而Argonaute2及成纤维细胞生长因子受体编码基因仅对nanos阴性细胞的功能维持必不可少。本研究结果表明，一套基于干细胞的古老发育程序或促成了寄生扁虫复杂生命周期的演化。
实验设计概要：从约10000只刚孵化的毛蚴，或转化后48小时的胞蚴中提取总RNA。