The first cell atlas of an important stage of life of Schistosoma mansoni, a parasitic worm that poses a threat to hundreds of millions of people each year, was developed by researchers at the Wellcome Sanger Institute and their colleagues.
The study, published today (18 December 2020) in Nature Communication, identified 13 specific cell types within the worm at the beginning of its development into a dangerous parasite, introducing new cell types in the nervous and muscular systems. The atlas provides a guidebook for a better understanding of S. mansoni biology that will allow you to explore new vaccines and treatments.
S. mansoni has a complex life cycle that begins when larval forms of the parasite emerge from snails into rivers and lakes. These larvae then enter humans through the skin after contact with diseased water. Once inside the body, the parasite begins the so-called intra-mammalian cycle of its life cycle, going through a series of developmental movements as it enters the adult level.
Adult worms live in human blood vessels and reproduce, releasing eggs from the body into water to continue their life cycle. But some of the eggs are still locked in the body, leading to the disease schistosomiasis.
Schistosomiasis is a debilitating long-term illness that can lead to inability to work, organ damage and death. It affects hundreds of millions of people every year, especially in sub-Saharan Africa, * and is listed by the World Health Organization (WHO) as one of the most neglected tropical diseases. Currently, there is only one drug available to treat the disease, but this is unsuitable for use in very young children and there are fears that over-reliance on one treatment will allow the parasites to become infected. against the drug.
Researchers have been looking at ways to find new drug targets, but so far there has not been a high understanding of the biology of the disc.
This new study attempted to map all cells in the first stage within the mammalian of the parasite using single-cell technology, which identifies different cell types present in growth or loom.
The early-stage parasites were broken down into individual cells identified by a single-cell RNA sequence by scientists at the Wellcome Sanger Institute. The data were then analyzed to identify cell types according to the genes expressed by individual cells, and where in the body those cells were located.
The team identified 13 specific cell types, including previously unrecognized cell types in the nervous system and parenchymal system **. Separate fluorescent probes were performed for genes expressed specifically according to each cell type. Scientists at the Morgridge Research Institute in the US used these probes to determine the position of cells found inside whole parasites under the microscope.
Dr Carmen Diaz Soria, the first author of the study from the Wellcome Sanger Institute, said: “Although our understanding of Schistosoma mansoni has come a long way in recent years, we have not been able to identify targets that lead to viable vaccine. cell RNA sequences provide a whole new level of biological detail, including previously unknown cell types, which allows us to better understand each cell number in the parasite. “
To identify new drug targets, researchers typically look for differences between a pathogen and its human host. However, S. mansoni is much closer to us in terms of evolution than most major parasites, such as those that cause malaria. It is hoped that these findings will reveal areas of the parasite’s genetic code that are sufficiently different from our own to become operational treatment targets.
Dr. Jayhun Lee, the first author of the study from the Morgridge Research Institute, Wisconsin USA, said: “We found genes in the Schistosoma mansoni muscular system that may be specific to schistosomes. Because they are found in the These parameters but not in humans, are one treatment target that could be identified by the study.The muscle allows the parasite to travel through our bodies, so if we were able to block to enable that, we may be able to suspend its life cycle before reproduction occurs. “
The authors also shed light on the parenchymal tissue of S. mansoni, the ‘filler’ material that binds all the material of the parasite together. Previous studies had found it difficult to separate parenchymal cells for analysis. The cell atlas found that some genes that are important for the parasite to digest food are also associated with the parenchymal tension. Disturbing the way the parasite feeds by targeting these cells may be another way of healing.
Dr Matt Berriman, lead author of the paper from the Wellcome Sanger Institute, said: “Schistosomiasis is one of the most neglected parasitic diseases and a deeper understanding of the biology of the disc will help to reveal injuries that may one day be targeted by newcomers. remedies. We hope that this first-stage cell atlas within mammals of Schistosoma mansoni will provide researchers with valuable insights to help accelerate the development of new therapies and eradicate this parasite from the lives of hundreds of millions of affected people every year. “