Single cell transcriptomics of the human parasite Schistosoma mansoni first intra-molluscan stage reveals tentative tegumental and stem cell regulators

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Abstract

Background

Schistosomiasis is a major Neglected Tropical Disease, caused by the infection with blood flukes in the genus Schistosoma . To complete the life cycle, the parasite undergoes asexual and sexual reproduction within an intermediate snail host and a definitive mammalian host, respectively. The intra-molluscan phase provides a critical amplification step that ensures a successful transmission. However, the cellular and molecular mechanisms underlying the development of the intra-molluscan stages remain poorly understood.

Methods

S. mansoni mother sporocysts were dissociated into single cell suspensions, and live cells enriched and sequenced using the single cell 10X Genomics Chromium platform. We defined somatic and stem/germinal cell clusters, identified cell type-enriched Gene Ontology (GO) terms, and predicted transcription factor binding sites for key marker genes.

Results

Six cell clusters comprising stem/germinal, two tegument, muscle, neuron, and parenchyma were identified and validated by Fluorescence in situ Hybridisation (FISH). GO term analysis predicted key biological processes for each of the clusters. Using the Self-Assembling Manifold (SAM) algorithm, three sub-clusters were identified within the stem/germinal cell population. Furthermore, transcription factor binding sites and putative transcription factors were predicted for stem/germinal and tegument clusters.

Conclusions

We report a spatially validated single cell transcriptomic analysis of the first intra-molluscan stage of S. mansoni. Key cell regulators were identified, paving the way for future analyses to unveil their role during the parasite development and interaction with its intermediate host.

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