The retinoic acid family-like nuclear receptor SmRAR identified by single-cell transcriptomics of ovarian cells controls oocyte differentiation in Schistosoma mansoni

• Published in: Nucleic acids research 2024-12
• Main Authors: Moescheid, Max F, Lu, Zhigang, Soria, Carmen Diaz, Quack, Thomas, Puckelwaldt, Oliver, Holroyd, Nancy, Holzaepfel, Pauline, Haeberlein, Simone, Rinaldi, Gabriel, Berriman, Matthew, Grevelding, Christoph G
• Format: Article
• Language: English
• ISSN: 1362-4962; 1362-4962
• DOI: 10.1093/nar/gkae1228

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.