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A single-cell RNA-seq atlas of the pathogenic stage of Schistosoma mansoni identifies a key regulator of blood feeding

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Schistosoma mansoni

PROVIDER: GSE146737 | GEO | 2020/03/11

REPOSITORIES: GEO

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A single-cell RNA-seq atlas of <i>Schistosoma mansoni</i> identifies a key regulator of blood feeding.

Project description:Schistosomiasis is a neglected tropical disease that infects 240 million people. With no vaccines and only one drug available, new therapeutic targets are needed. The causative agents, schistosomes, are intravascular flatworm parasites that feed on blood and lay eggs, resulting in pathology. The function of the parasite's various tissues in successful parasitism are poorly understood, hindering identification of therapeutic targets. Using single-cell RNA sequencing (RNA-seq), we characterize 43,642 cells from the adult schistosome and identify 68 distinct cell populations, including specialized stem cells that maintain the parasite's blood-digesting gut. These stem cells express the gene hnf4, which is required for gut maintenance, blood feeding, and pathology in vivo. Together, these data provide molecular insights into the organ systems of this important pathogen and identify potential therapeutic targets.

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A single-cell RNA-seq atlas of the pathogenic stage of Schistosoma mansoni identifies a key regulator of blood feeding [scRNA-Seq]

Project description:In order to better understand the biology of adult schistosomes, we performed single-cell RNAseq on adult male, adult sexually-mature female, and adult virgin female parasites.

2020-03-11 | GSE146736 | GEO

A single-cell RNA-seq atlas of the pathogenic stage of Schistosoma mansoni identifies a key regulator of blood feeding [RNA-Seq]

Project description:The schistosome homolog of hnf4 is involved in parasite blood feeding and stem cell biology. In order to understand the function of hnf4, we performed RNAseq on either control(RNAi) or hnf4(RNAi) parasites to see the transcriptional consequences of hnf4 RNAi

2020-03-11 | GSE146735 | GEO

A single-cell RNA-seq atlas of the pathogenic stage of Schistosoma mansoni identifies a key regulator of blood feeding

Project description:A single-cell RNA-seq atlas of the pathogenic stage of Schistosoma mansoni identifies a key regulator of blood feeding

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A single-cell RNA-seq atlas of the pathogenic stage of Schistosoma mansoni identifies a key regulator of blood feeding [RNA-Seq]

Project description:A single-cell RNA-seq atlas of the pathogenic stage of Schistosoma mansoni identifies a key regulator of blood feeding [RNA-Seq]

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A single-cell RNA-seq atlas of the pathogenic stage of Schistosoma mansoni identifies a key regulator of blood feeding [scRNA-Seq]

Project description:A single-cell RNA-seq atlas of the pathogenic stage of Schistosoma mansoni identifies a key regulator of blood feeding [scRNA-Seq]

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Cytosine methylation regulates oviposition in the pathogenic blood fluke Schistosoma mansoni.

Project description:Similar to other metazoan pathogens, Schistosoma mansoni undergoes transcriptional and developmental regulation during its complex lifecycle and host interactions. DNA methylation as a mechanism to control these processes has, to date, been discounted in this parasite. Here we show the first evidence for cytosine methylation in the S. mansoni genome. Transcriptional coregulation of novel DNA methyltransferase (SmDnmt2) and methyl-CpG-binding domain proteins mirrors the detection of cytosine methylation abundance and implicates the presence of a functional DNA methylation machinery. Genome losses in cytosine methylation upon SmDnmt2 silencing and the identification of a hypermethylated, repetitive intron within a predicted forkhead gene confirm this assertion. Importantly, disruption of egg production and egg maturation by 5-azacytidine establishes an essential role for 5-methylcytosine in this parasite. These findings provide the first functional confirmation for this epigenetic modification in any worm species and link the cytosine methylation machinery to platyhelminth oviposition processes.

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Single-cell atlas of the first intra-mammalian developmental stage of the human parasite Schistosoma mansoni.

Project description: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.

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A gene expression atlas of adult Schistosoma mansoni and their gonads.

Project description:RNA-Seq has proven excellence in providing information about the regulation and transcript levels of genes. We used this method for profiling genes in the flatworm Schistosoma mansoni. This parasite causes schistosomiasis, an infectious disease of global importance for human and animals. The pathology of schistosomiasis is associated with the eggs, which are synthesized as a final consequence of male and female adults pairing. The male induces processes in the female that lead to the full development of its gonads as a prerequisite for egg production. Unpaired females remain sexually immature. Based on an organ-isolation method we obtained gonad tissue for RNA extraction from paired and unpaired schistosomes, with whole adults included as controls. From a total of 23 samples, we used high-throughput cDNA sequencing (RNA-Seq) on the Illumina platform to profile gene expression between genders and tissues, with and without pairing influence. The data obtained provide a wealth of information on the reproduction biology of schistosomes and a rich resource for exploitation through basic and applied research activities.

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The genome of the blood fluke Schistosoma mansoni.

Project description:Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.

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