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The retinoic acid family-like nuclear receptor SmRAR identified by single-cell transcriptomics of ovarian cells controls oocyte differentiation in Schistosoma mansoni.
Nucleic Acids Research ( IF 16.6 ) Pub Date : 2024-12-16 , DOI: 10.1093/nar/gkae1228
Max F Moescheid,Zhigang Lu,Carmen Diaz Soria,Thomas Quack,Oliver Puckelwaldt,Nancy Holroyd,Pauline Holzaepfel,Simone Haeberlein,Gabriel Rinaldi,Matthew Berriman,Christoph G Grevelding

Studies on transcription regulation in platyhelminth development are scarce, especially for parasitic flatworms. Here, we employed single-cell transcriptomics to identify genes involved in reproductive development in the trematode model Schistosoma mansoni. This parasite causes schistosomiasis, a major neglected infectious disease affecting >240 million people worldwide. The pathology of schistosomiasis is closely associated with schistosome eggs deposited in host organs including the liver. Unlike other trematodes, schistosomes exhibit distinct sexes, with egg production reliant on the pairing-dependent maturation of female reproductive organs. Despite this significance, the molecular mechanisms underlying ovary development and oocyte differentiation remain largely unexplored. Utilizing an organ isolation approach for S. mansoni, we extracted ovaries of paired females followed by single-cell RNA sequencing (RNA-seq) with disassociated oocytes. A total of 1967 oocytes expressing 7872 genes passed quality control (QC) filtering. Unsupervised clustering revealed four distinct cell clusters: somatic, germ cells and progeny, intermediate and late germ cells. Among distinct marker genes for each cluster, we identified a hitherto uncharacterized transcription factor of the retinoic acid receptor family, SmRAR. Functional analyses of SmRAR and associated genes like Smmeiob (meiosis-specific, oligonucleotide/oligosaccharide binding motif (OB) domain-containing) demonstrated their pairing-dependent and ovary-preferential expression and their decisive roles in oocyte differentiation of S. mansoni.

中文翻译:


通过卵巢细胞的单细胞转录组学鉴定的视黄酸家族样核受体 SmRAR 控制曼氏血吸虫的卵母细胞分化。



关于扁形蠕虫发育中转录调控的研究很少,尤其是对于寄生扁虫。在这里,我们采用单细胞转录组学来鉴定吸虫模型中参与生殖发育的基因 曼氏血吸虫.这种寄生虫会导致血吸虫病,这是一种被忽视的主要传染病,影响全球 >2.4 亿人。血吸虫病的病理学与沉积在宿主器官(包括肝脏)中的血吸虫卵密切相关。与其他吸虫不同,血吸虫表现出不同的性别,卵的产生依赖于女性生殖器官的配对依赖性成熟。尽管具有这一重要意义,但卵巢发育和卵母细胞分化的分子机制在很大程度上仍未得到探索。利用曼氏血吸虫的器官分离方法,我们提取了配对雌性的卵巢,然后对解离的卵母细胞进行单细胞 RNA 测序 (RNA-seq)。共有 1967 个卵母细胞表达 7872 个基因通过质量控制 (QC) 过滤。无监督聚类揭示了四个不同的细胞簇:体细胞、生殖细胞和后代、中间和晚期生殖细胞。在每个簇的不同标记基因中,我们确定了视黄酸受体家族迄今为止未表征的转录因子 SmRAR。SmRAR 和相关基因如 Smmeiob (减数分裂特异性、寡核苷酸/寡糖结合基序 (OB) 结构域)的功能分析表明了它们的配对依赖性和卵巢优先表达以及它们在曼氏血吸虫卵母细胞分化中的决定性作用。
更新日期:2024-12-16
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