A single-cell RNA-seq atlas of the pathogenic stage of Schistosoma mansoni identifies a key regulator of blood feeding [scRNA-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Schistosoma mansoni
PROVIDER: GSE146736 | GEO | 2020/03/11
REPOSITORIES: GEO
Similar Datasets
Project description:We present a comparative analysis of sex-specific tegument proteins of paired or virgin Schistosoma mansoni. By apply a new and highly sensitive workflow, detection of even low abundance proteins from the worm was achieved Therefore, a streptavidin-biotin affinity purification technique in combination with single pot solid-phase enhanced sample preparation was established for subsequent LC-MS/MS analysis. We were able to identify 1519 tegument proteins for male and female as to virgin and paired worms. Sex-specific proteins were screened, present in both virgin and paired adult schistosomes to reduce the impact of mating. Bioinformatic analysis revealed an involvement of female-specific tegument proteins in signaling pathways of cellular processes and antioxidant mechanisms. Male-specific proteins were found to be enriched in processes linked to phosphorylation and signal transduction. This suggests a task sharing between the sexes that might be necessary for survival in the host. Our datasets provide a basis for further studies to understand and ultimately decipher the strategies of the two worm sexes to evade the immune system.
2022-05-20 | PXD031167 | Pride
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
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.
2011-05-27 | GSE29535 | GEO
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:We report differences in gene expression between the anterior and posterior of female Schistosoma mansoni parasites
2016-03-08 | GSE78967 | GEO
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:Intestinal Schistosomiasis, caused by the helminth Schistosoma mansoni, results in fibroproliferative disease triggered by liver trapped parasite eggs. Characteristic of the infection is a chronic course of disease with progressive periportal fibrosis, spleno- and hepatomegaly, and portal hypertension. Despite significant progress in understanding the complex immunological processes involved in the host-pathogen relationship, there is currently no effective vaccine against the infection nor antifibrotic drugs, increasing the pressure to find new targets for schistosome drugs and vaccine candidates. We have recently reported that infection with male schistosomes can attenuate reinfections, while female schistosomes appear to weaken the host immune system. To decipher the underlying mechanisms of differential immunogenicity of female and male worms, we performed a comparative transcriptomic analysis of splenic tissue from unisexually and bisexually infected mice. We identified a total of 1293, 512 and 4062 genes, respectively, that were differentially expressed in the group of male-only (M), female-only (F) or bisexually (MF) infected mice compared to naive controls. Bisexual infection and infection with male worms showed the marked effects on host immune response, erythrocyte homeostasis, lipoprotein metabolism and cell cycle processes compared to the infection with female worms. Furthermore, we could show that both worm sexes trigger immune responses in an egg-independent manner, with a non-polarized Th1 and Th2 response, with female worms having a lower regulatory influence than males.
2022-06-16 | GSE197804 | GEO
Project description:42 days old adult worms: adult worms vs. adult worms (self-self)
| PRJNA98145 | ENA
Project description:RNA-seq data: Molluscicide impedes development of Schistosoma mansoni cercariae into adult parasites
| PRJNA395143 | ENA
Project description:RNA-seq data: Molluscicide impedes development of Schistosoma mansoni cercariae into adult parasites
| PRJNA395144 | ENA