Schistosomes infect over 200 million people. The prodigious egg output of these parasites is the sole driver of pathology due to infection, yet our understanding of sexual reproduction by schistosomes is limited because normal egg production is not sustained for more than a few days in vitro. Here, we describe culture conditions that support schistosome sexual development and sustained egg production in vitro. Female schistosomes rely on continuous pairing with male worms to fuel the maturation of their reproductive organs. Exploiting these new culture conditions, we explore the process of male-stimulated female maturation and demonstrate that physical contact with a male worm, and not insemination, is sufficient to induce female development and the production of viable parthenogenetic haploid embryos. We further report the characterization of a nuclear receptor (NR), which we call Vitellogenic Factor 1 (VF1), that is essential for female sexual development following pairing with a male worm. Taken together, these results provide a platform to study the fascinating sexual biology of these parasites on a molecular level, illuminating new strategies to control schistosome egg production.

Schistosomes cause significant morbidity and mortality in millions of the world's poorest people. While parasite egg-induced inflammation is the primary driver of host pathology, relatively little is known at the molecular level about the organ systems that participate in schistosome egg production (i.e., testes, ovaries and vitellaria). Here we use transcriptional profiling and in situ hybridization to characterise the vitellarium of Schistosoma mansoni. We uncovered several previously uncharacterised vitellaria-specific factors and defined molecular markers for various stages in the vitellocyte differentiation process. These data provide the framework for future in-depth molecular studies exploring the biology of this important parasite organ.

Eggs produced by the mature female parasite are responsible for the pathogenesis and transmission of schistosomiasis. Female schistosomes rely on a unique male-induced strategy to accomplish reproductive development, a process that is incompletely understood. Here we map detailed transcriptomic profiles of male and femaleSchistosoma japonicumacross eight time points throughout the sexual developmental process from pairing to maturation. The dynamic gene expression pattern data reveal clear sex-related characteristics, indicative of an unambiguous functional division between males and females during their interplay. Cluster analysis,in situhybridization and RNAi assays indicate that males likely use biogenic amine neurotransmitters through the nervous system to control and maintain pairing with females. In addition, the analyses indicate that reproductive development of females involves an insect-like hormonal regulation. These data sets and analyses serve as a foundation for deeper study of sexual development in this pathogen and identification of novel anti-schistosomal interventions.

Schistosome biology illuminated: Schistosomiasis is caused by a parasitic flatworm about which little is known. Therefore, options to combat human disease caused by schistosome infection are limited. To aid in our quest to develop treatments, two studies undertook molecular investigations of the parasite Schistosoma mansoni . By generating a single-cell atlas, Wendt et al. identified the developmental trajectory of the flatworm, including the blood-feeding gut required for its survival in the host. From these data, they found a gene required for gut development that, when knocked out through RNA interference, confers reduced pathology in infected mice. Wang et al. performed a large-scale RNA interference survey of S. mansoni and identified an essential pair of protein kinases that can be targeted by approved pharmacological intervention (see the Perspective by Anderson and Duraisingh). These molecular investigations add to our understanding of the schistosome parasite and provide biological information that may help to combat this neglected tropical disease. Science , this issue p. 1644 , p. 1649 ; see also p. 1562

Schistosoma japonicum is a parasitic flatworm that causes human schistosomiasis, which is a significant cause of morbidity in China and the Philippines. A single draft genome was available for S. japonicum, yet this assembly is very fragmented and only covers 90% of the genome, which make it difficult to be applied as a reference in functional genome analysis and genes discovery. In this study, we present a high-quality assembly of the fluke S. japonicum genome by combining 20 G (~53X) long single molecule real time sequencing reads with 80 G (~ 213X) Illumina paired-end reads. This improved genome assembly is approximately 370.5 Mb, with contig and scaffold N50 length of 871.9 kb and 1.09 Mb, representing 142.4-fold and 6.2-fold improvement over the released WGS-based assembly, respectively. Additionally, our assembly captured 85.2% complete and 4.6% partial eukaryotic Benchmarking Universal Single-Copy Orthologs. Repetitive elements account for 46.80% of the genome, and 10,089 of the protein-coding genes were predicted from the improved genome, of which 96.5% have been functionally annotated. Lastly, using the improved assembly, we identified 20 significantly expanded gene families in S. japonicum, and those genes were primarily enriched in functions of proteolysis and protein glycosylation. Using the combination of PacBio and Illumina Sequencing technologies, we provided an improved high-quality genome of S. japonicum. This improved genome assembly, as well as the annotation, will be useful for the comparative genomics of the flukes and more importantly facilitate the molecular studies of this important parasite in the future. Schistosomiasis is an acute and chronic disease that remains one of the most prevalent and serious of the parasitic diseases in the world. Three major Schistosoma species cause human schistosomiasis, including Schistosoma japonicum, S. mansoni and S. haematobium. However, the three schistosome references or draft genomes were released in the last decade, which greatly facilitate the progress in the whole research field of schistosome. However, limited by the sequencing technique and mixture samples at that time, only a genome draft was suppled to S. japonicum, which is fragmented and difficult to be a reference in functional genome analysis and gene discovery. Here, using the combination of PacBio and Illumina Sequencing technologies, we present a high-quality assembly of S. japonicum with contig and scaffold N50 length of 871.9 kb and 1.09 Mb, representing 142.4-fold and 6.2-fold improvement over the released WGS-based assembly, respectively. The assembly genome with high quality will certainly supply a new reference genome of S. japonicum and be beneficial to functional genomic and comparative genomics of schistosome, as well as other helminths.