A single-cell atlas of the miracidium larva of the human blood fluke Schistosoma mansoni: cell types, developmental pathways and tissue architecture

Abstract

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 we identified every cell in the whole organism revealing the organisation of the miracidium, and present here the single cell atlas. Because of its simplicity, the miracidium provides a tractable system to understand the development of Schistosoma mansoni as it increases in complexity around the life cycle.

James Cotton

Professor

My research interests are in the genomics, and particularly population genomics of parasites, particularly those that cause neglected tropical diseases