Single-cell analysis ofSchistosoma mansonireveals a conserved genetic program controlling germline stem cell fate

Abstract

<jats:title>Abstract</jats:title><jats:p>Schistosomes are parasitic flatworms causing one of the most prevalent infectious diseases from which millions of people are currently suffering. Their germline outputs many fertilized eggs, which are both the transmissible agents and the cause of the infection-associated pathology. Given its significance, the schistosome germline has been a research focus for more than a century. Nonetheless, little is known about the molecular mechanisms that regulate its development. Here, we construct a transcriptomic cell type atlas of juvenile schistosomes. This allows us to capture germline stem cells (GSCs) during <jats:italic>de novo</jats:italic> gonadal development. We identify a genetic program that balances the fate of GSC between proliferation and differentiation. This program is controlled by <jats:italic>onecut</jats:italic>, a homeobox transcription factor, and <jats:italic>boule</jats:italic>, an mRNA binding protein. Evaluating this genetic program in schistosome’s free-living evolutionary cousin, the planarian, shows that this germline-specific regulatory program is conserved but its function has changed significantly during evolution.</jats:p>

Mapping single-cell atlases throughout Metazoa unravels cell type evolution

“…Tissue type annotations are adopted from the S. mediterranea atlas (Fincher et al, 2018). The schistosome atlas was collected from juvenile worms, which we found to contain neoblasts with an abundance comparable to that of planarian neoblasts (Li et al, 2020) interquartile ranges of the mean standardized expressions of genes in hydra and planarian stem cells/progenitors that are conserved across all invertebrate species in this study. Planarian progenitors: piwi+ cells that cluster with differentiated tissues in Fincher et al (Fincher et al, 2018).…”

“…To test if we can identify homologous cell types in animals with radically different body plans, we mapped the cell atlases of two flatworms, the planarian Schmidtea mediterranea (Fincher et al, 2018), and the trematode Schistosoma mansoni, which we collected recently (Li et al, 2020). They represent two distant lineages within the same phylum but have remarkably distinct body plans and autecology (Laumer et al, 2015;Littlewood & Waeschenbach, 2015).…”

“…The annotations provided by their respective studies were used to label the cells in the Spongilla, Hydra, and mouse atlases. To annotate the schistosome cells, we used known marker genes to annotate the main schistosome tissue types (Li et al, 2020). Annotations for all single cells in all datasets are provided in Supplementary Table 1.…”

Trematode Proteomics: Recent Advances and Future Directions

“…Future research may also move away from bulk proteomics experiments (which yield the average protein composition of a range of cells) to single-cell proteomics, which would reveal the cellular heterogeneity that exists in parasite tissues. Single-cell transcriptomics has already been employed in schistosomes to characterise different cell types based on their gene expression patterns and to track cell fates [ 78 , 79 , 80 ]. Single-cell proteomics by mass spectrometry (SCP-MS) is based on a similar starting principle where tissue is dissociated into a single-cell suspension from which cells are separated using fluorescent-activated cell sorting (FACS) based on cell size and shape or specific surface proteins [ 81 ].…”

The esophageal gland mediates host immune evasion by the human parasiteSchistosoma mansoni

“…Failure at any step would disrupt the life cycle, yet it manages these challenges, even in the face of the host’s immune system ( 4 , 5 ). Recent work has identified heterogeneous populations of schistosome stem cells ( 6 – 10 ) and described their roles in asexual reproduction ( 7 , 11 ), tegument (the parasite’s outer surface) production during homeostasis ( 12 , 13 ), and germ cell development ( 7 , 8 , 10 , 14 ). Thus, stem cells help drive schistosome viability and transmission.…”