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Attenborough, T.

Publications and source records attributed to Attenborough, T..

2 recordsLinked to original sources

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

BackgroundSchistosomiasis 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. MethodsS. 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. ResultsSix 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. ConclusionsWe 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.

developmental biology↗

A single-cell atlas of the free-living miracidium larva of Schistosoma mansoni

Schistosomes are parasitic flatworms that cause the water-borne disease schistosomiasis, affecting millions of people worldwide. The miracidium larva of schistosomes represents the first post-embryonic stage of development and is critical to transmission. After hatching, a miracidium infects a freshwater snail and transforms into a mother sporocyst, where its stem cells generate daughter sporocysts that give rise to many human-infective cercariae larvae. To understand this important life cycle stage at the cellular and molecular levels, we have used single-cell RNA sequencing, in situ hybridisation and image analysis to create a whole-body cell atlas of the miracidium larva of Schistosoma mansoni. Our atlas shows that each miracidium is composed of [~]365 cells and 19 transcriptionally distinct cell types. We show that 93% of miracidium cells are somatic (57% neural, 19% muscle, 13% epidermal (tegument), 2% parenchyma, 2% protonephridia), and the remaining 7% are stem cells. Cellular diversity within tissue types is revealed, and is highest in neurons. There are two stem cell populations, and they show different activation and potency states. Trajectory analysis indicates that one stem cell population is the origin of the tegument lineage and the other likely contains pluripotent cells. Furthermore, each of these stem populations is transcriptionally distinct based on sex-linked gene expression in male and female larvae. Through single cell transcriptomics and in-situ hybridisation we identified every cell in the whole organism revealing the organisation of the miracidium. This single cell atlas provides the foundation to understand the development and interaction of cell types and tissues as they change over a life cycle that is characterised by complex morphological changes.

genomics↗