The stage- and sex-specific transcriptome of the human parasite Schistosoma mansoni

Abstract

The flatworm Schistosoma mansoni is an important but neglected pathogen that causes the disease schistosomiasis in millions of people worldwide. The parasite has a complex life cycle, undergoing sexual reproduction in a mammalian host and asexual replication in a snail host. Understanding the molecular mechanisms that the parasite uses to transition between hosts and develop into dimorphic reproductively competent adults may reveal new strategies for control. We present the first comprehensive transcriptomic analysis of S. mansoni, from eggs to sexually naïve worms. Focusing on eight life stages spanning free-living water-borne and parasitic stages from both intermediate and definitive hosts, we have generated deep RNA-seq data for five replicates per group for a total of 75 data sets. The data were produced using a single approach to increase the accuracy of stage-to-stage comparisons and made accessible via a user-friendly tool to visualise and explore gene expression ( https://lifecycle.schisto.xyz/ ). These data are valuable for understanding the biology and sex-specific development of schistosomes and the interpretation of complementary genomic and functional genetics studies.

Fig. 1

Sampling key stages of the Schistosoma mansoni life cycle. The flatworm S. mansoni undergoes a series of morphological transitions throughout development, using waterborne stages to transition between the intermediate snail host and the definitive mammalian host. The life stages and sex (male, female, mixed) collected for this study are shown with their corresponding sex symbols. Eggs are produced from paired, sexually mature adults; however, sexually reproducing adults were not sequenced in this study. Figure adapted from Laura Olivares Boldú/Wellcome Connecting Science.

Fig. 2

Clustering of RNA-seq data by parasite sex and life stage. (a) A PCA plot of the 25% most variable genes was calculated by the coefficient of variation, highlighting life stage (colour) and sex (shape). (b) Clustering of samples based on Euclidean distance (Coefficient of Variation; CoV) of the 25% most variable genes. In both panels a and b, the colour is consistent with Fig. 1.

Fig. 3

Visualisation and exploration of stage and sex-specific RNA-seq data of Schistosoma mansoni. Demonstration of our easy-to-use data exploration tool https://lifecycle.schisto.xyz/ using S. mansoni Kunitz protease inhibitors as an example. (a,b) PCA plot of RNA-seq data coloured by life stage and parasite sex, which highlights male, female, and mixed-sex parasite data to provide context for gene-specific analyses. (c) A series of PCA plots show the expression of 11 S. mansoni Kunitz protease inhibitors. In panels a, b, and c, each point represents a single replicate (n = 75) and is coloured by log transcript per million values (log₂[TPM + 1]), with low expression represented by dark and high expression light colour. (d) A Heatmap of mean log₂(TPM + 1) expression for each gene is presented in panel c. Each point represents the mean TMP from five replicates, with the size of the point proportional to the number of replicates within a group with data.