Single-cell analysis reveals regulation of germline stem cell fate in the human parasite Schistosoma mansoni
Ontology highlight
ABSTRACT:
ORGANISM(S): Schistosoma mansoni
PROVIDER: GSE147355 | GEO | 2020/03/28
REPOSITORIES: GEO
Similar Datasets
Project description:Over 250 million people suffer from schistosomiasis, a tropical disease caused by parasitic flatworms known as schistosomes. To unravel the transcriptional signatures for the larval stage of this parasite, we perform single-cell RNA sequencing on two-day old schistosomula. We described 15 populations and spatially validated our results using FISH.
2020-11-07 | E-MTAB-9684 | biostudies-arrayexpress
Project description:RNA-seq experiments to identify gene expression changes following miracidia to sporocyst transformation in Schistosoma mansoni. Schistosomes infect hundreds of millions of people in the developing world. Transmission of these parasites relies on a stem cell-driven, clonal expansion of larvae inside a molluscan intermediate host. How this novel asexual reproductive strategy relates to current models of stem cell maintenance and germline specification is unclear. Here, we demonstrate that this proliferative larval cell population (germinal cells) shares some molecular signatures with stem cells from diverse organisms, in particular neoblasts of planarians (free-living relatives of schistosomes). We identify two distinct germinal cell lineages that differ in their proliferation kinetics and expression of a nanos ortholog. We show that a vasa PL10 homolog is required for proliferation and maintenance of both populations; whereas, argonaute2 and a fibroblast growth factor receptor-encoding gene are required only for nanos-negative cells. Our results suggest that an ancient stem cell-based developmental program may have enabled the evolution of the complex life-cycle of parasitic flatworms. Total RNA was purified from ~10,000 freshly hatched miracidia or sporocysts 48 h post-transformation.
2013-12-31 | E-GEOD-48282 | biostudies-arrayexpress
Project description:RNA-seq experiments to identify gene expression changes following miracidia to sporocyst transformation in Schistosoma mansoni. Schistosomes infect hundreds of millions of people in the developing world. Transmission of these parasites relies on a stem cell-driven, clonal expansion of larvae inside a molluscan intermediate host. How this novel asexual reproductive strategy relates to current models of stem cell maintenance and germline specification is unclear. Here, we demonstrate that this proliferative larval cell population (germinal cells) shares some molecular signatures with stem cells from diverse organisms, in particular neoblasts of planarians (free-living relatives of schistosomes). We identify two distinct germinal cell lineages that differ in their proliferation kinetics and expression of a nanos ortholog. We show that a vasa PL10 homolog is required for proliferation and maintenance of both populations; whereas, argonaute2 and a fibroblast growth factor receptor-encoding gene are required only for nanos-negative cells. Our results suggest that an ancient stem cell-based developmental program may have enabled the evolution of the complex life-cycle of parasitic flatworms.
2013-12-31 | GSE48282 | GEO
Project description:Schistosomiasis is a chronic neglected tropical disease caused by digenetic parasitic flatworms of the genus Schistosoma. The disease is estimated to affect over 206 million people, the majority of whom live in Africa where Schistosoma mansoni and Schistosoma japonicum are the major causative agents. While a number of drugs have been used to treat schistosomiasis, praziquantel (PZQ) is the only one that is widely available, relatively cheap, and easy to use. The reliance on a single drug for the treatment of such a prevalent disease is a cause for concern due to the potential for resistance to render PZQ ineffective. In this study we examine the transcriptome of three generations of a laboratory strain of S. mansoni (PR1) whose susceptibility to PZQ has been diminished across 9 passages through exposure to increasing sub-lethal doses of the drug. Miracidial susceptibility was significantly reduced after exposure to 2 x 50 mg/Kg PZQ during the first passage. Susceptibility of worms in vivo was first assessed during passage 5 when mice infected with PZQ-selected schistosomes were dosed with a lethal dose of 3 x 300 mg/Kg PZQ resulting in only a 10% reduction in worm number compared to control treatment. The emergence of reduced sensitivity was marked by a shift in sex ratio from a predominantly male to female population, a reduction in the length of females and ultimately the loss of the PZQ-selected line after passage 9, perhaps due to a selection induced fitness cost. Analysis of differentially regulated transcripts did not suggest that any particular gene product or pathway was associated with drug resistance suggesting either a loss of function mutation to a single gene or an epistatic interaction of multiple gene products.
2019-02-26 | GSE120682 | GEO
Project description:Study description:This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/ Schistosomes are blood dwelling digenean trematodes that mature as adults in the intestinal or urinary veins, predominantly of mammals. Adult female Schistosomes produce eggs of which approximately 40% fail to pass into faeces or urine (species-dependent) but are dispersed by the blood stream into different organs where they provoke severe inflammation. This parasitic infection is known as schistosomiasis and considered by the WHO as the second most socioeconomically devastating parasitic disease, next only to malaria, with hundreds of millions infected worldwide. As the eggs represent the causative pathogenic agents, the understanding of egg forming processes, and therefore of the schistosomal reproductive biology in general, is of fundamental interest. Additionally the differences between immature (pre-mating) and mature (post-mating) adult worms are of significant interest; adults only reach maturity upon mating. Trasncriptomic sequencing of gonad-specific cellular material will help to unravel signal transduction cascades involved in e.g. gametogenesis and/or vitellogenesis. This project aims to characterize the transcriptome profiles of immature and mature adult ovaries and adult testes.
2016-07-05 | E-ERAD-516 | biostudies-arrayexpress
Project description:stk25 and tao genes came out of an RNAi screen in the parasitic flatworm Schistosoma mansoni, and these genes shared a similar knockdown phenotype. To test for a functional relationship, we compared transcriptomes of early knockdown worms for each gene, compared to mock controls.
2020-03-11 | GSE146720 | GEO
Project description:Schistosomiasis is a chronic parasitic disease that affects more that 230 million people worldwide. In the Americas, it caused by the blood flook Schistosoma mansoni. This parasite has a complex life cycle with two intermediary hosts. When infecting mammals, schistosomes cause an intense immune response to the presence of the different stages of the parasite within the host. After maturation of the worms and commencing of the oviposition, some eggs are transported via circulation to the liver, where they elicit an exaggerated inflammatory response in the tissue. This could lead to the formation of granulomas and liver fibrosis and along with this, the developent of hepatosplenomegaly and in the worst scenario could lead to the dead of the patient. In this project, we aim to make a shotgun evaluation of the proteome from splenocytes in a mice model, in order to identify novel molecular signatures associated with the immune respose to the presence of the parasite in the hosts.
2019-02-13 | PXD011153 | Pride
Project description:In the complex lifecycle of schistosomes, four developmental stages are closely associated with their definitive hosts: cercaria (infective stage), schistosomula and adult worm (parasitic stages), egg (pathogenic- and pathophoresis-stage). We have examined the gene expression profiles of Schistosoma japonicum in the four developmental stages. Genes with different expression patterns were identified and the information obtained will help indentify new anti-schistosomal intervention targets in the future.
2017-02-09 | GSE57143 | GEO
Project description:Schistosomiasis is frequently detected in persons entering Europe. In 2017, we detected a Schistosoma mansoni-Schistosoma haematobium hybrid parasite infection in a migrant boy from Côte d'Ivoire entering France. Because such parasites might be established in Europe, as illustrated by an outbreak on Corsica Island, vectors of these parasites should be investigated.
| S-EPMC6346478 | biostudies-literature
Project description:Schistosoma mansoni is one of the most common etiological agents responsible for the disease schistosomiasis. More than 200 million people suffer from this disease making it the most severe tropical disease after malaria in terms of morbidity. Praziquantel (PZQ) is the treatment of choice for schistosomiasis and has been used almost exclusively to treat the disease since the 1970s. However, while the drug is lethal for sexually mature schistosomes, it is ineffective against juveniles. Thus, while morbidity can be eased, a cure is difficult to achieve. As a result there is an urgent need to develop a new generation of anti-schistosomal drugs, a task that will be made easier by understanding the mechanism of action of PZQ. As yet, neither the molecule to which PZQ binds nor the means by which it kills mature schistosomes is known. The overarching aim of this study was to understand the molecular basis of PZQ sensitivity in S. mansoni. We believe that juvenile worms survive PZQ treatment in vivo due to the induction of, as yet, unidentified protective molecular pathways. To address this hypothesis juvenile and adult PR1 S. mansoni were treated in vitro with sub-lethal concentrations of PZQ. mRNA was extracted from replicate samples, cRNA prepagreen and labeled with cyanine dyes for analysis using a 44K S. mansoni microarray. The data was then analyzed using Genespring. Our findings suggest that a number of genes associated with drug transport, iron homeostasis and apoptosis are induced in juvenile but not adult schistosomes and that this allows the juvenile worms to protect themselves against the lethal effects of PZQ long enough for the drug to be metabolized by the human host. 42 days post exposure (DPE) male schistosomes were exposed to 0 and 1 µg/mL praziquantel (PZQ) for 1 or 20 h and 10 µg/mL PZQ for 1 h. 42 DPE female schistosomes were exposed to 0, 1 and 10 µg/mL PZQ for 20 h. 28 DPE mixed-sex schistosomes were exposed to 0, 1 and 10 µg/mL PZQ for 1 and 20 h. All experiments were performed in biological triplicates. The 0 µg/mL PZQ exposures were used as controls to the appropriate groups and a universal reference was used in all experiments that was comprised of RNA derived from 100 mixed sex, unexposed 42 DPE schistosomes spiked with 0.5 % (v/v) RNA isolated from 42 DPE mixed sex worms exposed to 10 µg/mL PZQ, 0.5 % (v/v) RNA isolated from 28 DPE worms exposed to 10 µg/mL PZQ and 0.5 % (v/v) RNA isolated from 28 DPE worms unexposed to PZQ. Transcriptional response to praziquantel exposure by time and concentration
2011-05-27 | E-GEOD-29535 | biostudies-arrayexpress