Abstract
Over 250 million people suffer from schistosomiasis, a tropical disease caused by parasitic flatworms known as schistosomes. Humans become infected by free-swimming, water-borne larvae, which penetrate the skin. The earliest intra-mammalian stage, called the schistosomulum, undergoes a series of developmental transitions. These changes are critical for the parasite to adapt to its new environment as it navigates through host tissues to reach its niche, where it will grow to reproductive maturity. Unravelling the mechanisms that drive intra-mammalian development requires knowledge of the spatial organisation and transcriptional dynamics of different cell types that comprise the schistomulum body. To fill these important knowledge gaps, we perform single-cell RNA sequencing on two-day old schistosomula of Schistosoma mansoni. We identify likely gene expression profiles for muscle, nervous system, tegument, oesophageal gland, parenchymal/primordial gut cells, and stem cells. In addition, we validate cell markers for all these clusters by in situ hybridisation in schistosomula and adult parasites. Taken together, this study provides a comprehensive cell-type atlas for the early intra-mammalian stage of this devastating metazoan parasite.
Highlights
Over 250 million people suffer from schistosomiasis, a tropical disease caused by parasitic flatworms known as schistosomes
10X Chromium barcoded gel beads cercariae infection schistosomula live single cells fluorescein diacetate hepatic perfusion 7 weeks post-infection validation of scRNA-Seq and spatial mapping using in situ hybridisation (ISH)
We performed single-cell RNA sequencing of schistosomula collected two days after mechanically detaching the tail from free-living motile larvae (Fig. 1a)
Summary
Over 250 million people suffer from schistosomiasis, a tropical disease caused by parasitic flatworms known as schistosomes. Throughout the rest of the organism’s life span in the definitive host, a population of subtegumental progenitor cells continuously replenish the tegument, allowing the parasite to survive for decades[6,7] The schistosomula make their way into blood or lymphatic vessels and, one week after infection, reach the lung capillaries[8]. Dramatic changes to the parasite are required that include posterior growth, remodelling of the musculature[10] and nervous system[11,12] as well as the development of the gonads[13] and gut[14] This extensive tissue development starts in the schistosomula, with stem cells driving these transitions[7,15,16]. Adults anatomical features cephalic ganglia oesophagus gut primordia ventral sucker germinal cells cells oil identification of cluster discriminating markers in whole larvae b parenchymal 2 parenchymal 1
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