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Background: While considerable genomic and transcriptomic data are available for Schistosoma mansoni, many of its genes lack significant annotation. A transcriptomic study of individual tissues and organs of schistosomes could play an important role in functional annotation of the unknown genes, particularly by providing rapid localisation data and thus giving insight into the potential roles of these molecules in parasite development, reproduction and homeostasis, and in the complex host-parasite interaction. Methodology/Principal Findings: Quantification of gene expression in tissues of S. mansoni was achieved by a combination of laser microdissection microscopy (LMM) and oligonucleotide microarray analysis. We compared the gene expression profile of the adult female gastrodermis and male and female reproductive tissues with whole worm controls. The results revealed a total of 393 genes (contigs) that were up-regulated two-fold or more in the gastrodermis, 4,450 in the ovary, 384 in the vitelline tissues of female parasites, and 2,171 in the testes. We have also supplemented these data with the identification of highly expressed genes in different regions of manually dissected male and female S. mansoni. Though relatively crude, this dissection strategy provides low resolution localisation data for critical regions of the adult parasites that are not amenable to LMM isolation. Conclusions: This is the first detailed transcriptomic study of the reproductive tissues and gastrodermis of S. mansoni. The results obtained will help direct future research on the functional aspects of these tissues, expediting the characterisation of currently unannotated gene products of S. mansoni and the discovery of new drug and vaccine targets. Author Summary: There is currently only one drug available for treatment of schistosomiasis mansoni and no vaccine. The searches for possible new drug and vaccine candidates remain two major areas of current research in schistosomiasis. There are considerable amounts of data available on the genomics, transcriptomics and proteomics of Schistosoma mansoni from which useful candidates for future drug and vaccine development can be identified. Arranging these data into a biologically relevant context through the characterisation of gene expression profiles of the different tissues of this complex metazoan parasite, is an essential step in identifying molecules with potential therapeutic value. We have used laser microdissection microscopy and microarray analysis to show that many tissue-specific genes are up-regulated in the digestive and reproductive tissues of S. mansoni. This new knowledge provides an avenue to investigate the molecular components associated with fundamental aspects of schistosome biology. [ABSTRACT FROM AUTHOR]

Background: While considerable genomic and transcriptomic data are available for Schistosoma mansoni, many of its genes lack significant annotation. A transcriptomic study of individual tissues and organs of schistosomes could play an important role in functional annotation of the unknown genes, particularly by providing rapid localisation data and thus giving insight into the potential roles of these molecules in parasite development, reproduction and homeostasis, and in the complex host-parasite interaction. Methodology/Principal Findings: Quantification of gene expression in tissues of S. mansoni was achieved by a combination of laser microdissection microscopy (LMM) and oligonucleotide microarray analysis. We compared the gene expression profile of the adult female gastrodermis and male and female reproductive tissues with whole worm controls. The results revealed a total of 393 genes (contigs) that were up-regulated two-fold or more in the gastrodermis, 4,450 in the ovary, 384 in the vitelline tissues of female parasites, and 2,171 in the testes. We have also supplemented these data with the identification of highly expressed genes in different regions of manually dissected male and female S. mansoni. Though relatively crude, this dissection strategy provides low resolution localisation data for critical regions of the adult parasites that are not amenable to LMM isolation. Conclusions: This is the first detailed transcriptomic study of the reproductive tissues and gastrodermis of S. mansoni. The results obtained will help direct future research on the functional aspects of these tissues, expediting the characterisation of currently unannotated gene products of S. mansoni and the discovery of new drug and vaccine targets. [ABSTRACT FROM AUTHOR]

Background: Schistosomes cause more mortality and morbidity than any other human helminth, but control primarily relies on a single drug that kills adult worms. The newly transformed schistosomulum stage is susceptible to the immune response and is a target for vaccine development and rational drug design. Methodology/Principal Findings: To identify genes which are up-regulated during the maturation of Schistosoma mansoni schistosomula in vitro, we cultured newly transformed parasites for 3 h or 5 days with and without erythrocytes and compared their transcriptional profiles using cDNA microarrays. The most apparent changes were in the up-regulation of genes between 3 h and 5 day schistosomula involved in blood feeding, tegument and cytoskeletal development, cell adhesion, and stress responses. The most highly up-regulated genes included a tegument tetraspanin Sm-tsp-3 (1,600-fold up-regulation), a protein kinase, a novel serine protease and serine protease inhibitor, and intestinal proteases belonging to distinct mechanistic classes. The inclusion of erythrocytes in the culture medium resulted in a general but less pronounced increase in transcriptional activity, with the highest up-regulation of genes involved in iron metabolism, proteolysis, and transport of fatty acids and sugars. Conclusions: We have identified the genes that are up-regulated during the first 5 days of schistosomula development in vitro. Using a combination of gene silencing techniques and murine protection studies, some of these highly up-regulated transcripts can be targeted for future development of new vaccines and drugs. Author Summary: Schistosome blood flukes cause more mortality and morbidity than any other human worm infection, but current control methods primarily rely on a single drug. There is a desperate need for new approaches to control this parasite, including vaccines. People become infected when the free-swimming larva, the cercaria, enters through the skin and becomes the schistosomulum. Schistosomula are susceptible to immune responses during their first few days in the host before they become adult parasites. We characterised the genes that these newly transformed parasites switch on when they enter the host to identify molecules that are critical for survival in the human host. Some of these highly up-regulated genes can be targeted for future development of new vaccines and drugs. [ABSTRACT FROM AUTHOR]

Background: Schistosomes cause more mortality and morbidity than any other human helminth, but control primarily relies on a single drug that kills adult worms. The newly transformed schistosomulum stage is susceptible to the immune response and is a target for vaccine development and rational drug design. Methodology/Principal Findings: To identify genes which are up-regulated during the maturation of Schistosoma mansoni schistosomula in vitro, we cultured newly transformed parasites for 3 h or 5 days with and without erythrocytes and compared their transcriptional profiles using cDNA microarrays. The most apparent changes were in the up-regulation of genes between 3 h and 5 day schistosomula involved in blood feeding, tegument and cytoskeletal development, cell adhesion, and stress responses. The most highly up-regulated genes included a tegument tetraspanin Sm-tsp-3 (1,600-fold up-regulation), a protein kinase, a novel serine protease and serine protease inhibitor, and intestinal proteases belonging to distinct mechanistic classes. The inclusion of erythrocytes in the culture medium resulted in a general but less pronounced increase in transcriptional activity, with the highest up-regulation of genes involved in iron metabolism, proteolysis, and transport of fatty acids and sugars. Conclusions: We have identified the genes that are up-regulated during the first 5 days of schistosomula development in vitro. Using a combination of gene silencing techniques and murine protection studies, some of these highly up-regulated transcripts can be targeted for future development of new vaccines and drugs. [ABSTRACT FROM AUTHOR]

Background: The functions of many schistosome gene products remain to be characterized. A major step towards elucidating function of these genes would be in defining their sites of expression. This goal is rendered difficult to achieve by the generally small size of the parasites and the lack of a body cavity, which precludes analysis of transcriptional profiles of the tissues in isolation. Methodology/Principal Findings: Here, we describe a combined laser microdissection microscopy (LMM) and microarray analysis approach to expedite tissue specific profiling and gene atlasing for tissues of adult female Schistosoma japonicum. This approach helps to solve the gene characterization "bottle-neck" brought about by acoelomy and the size of these parasites. Complementary RNA obtained after isolation from gastrodermis (parasite gut mucosa), vitelline glands and ovary by LMM were subjected to microarray analyses, resulting in identification of 147 genes upregulated in the gastrodermis, 4,149 genes in the ovary and 2,553 in the vitellaria. Conclusions: This work will help to shed light on the molecular pathobiology of this debilitating human parasite and aid in the discovery of new targets for the development of anti-schistosome vaccines and drugs. Author Summary: Schistosomes are parasitic worms responsible for important human diseases in tropical and developing nations. There is urgent need to develop new drugs and vaccines to augment current treatments for this disease. In recent years, concerted efforts by many laboratories have led to extensive genetic sequencing of the parasites, and the publication of genome sequence for two agents of schistosomiasis appears imminent. This genetic information has revealed many molecules expressed by the schistosome parasites for which no functional information is available. This lack of information extends to ignorance of where in the complex multicellular schistosome parasites the genes are expressed. We integrated two molecular and cellular techniques to address these knowledge gaps. We used laser microdissection microscopy to dissect small but highly important tissues involved in nutrition and reproduction from sections of female Schistosoma japonicum. From these dissected tissues we then used a broad molecular biology method to identify the multiple genes active in these tissues. Our approach has allowed us to formulate the basis of a "gene atlas" for schistosome parasites, defining the expression repertoire of specific tissues. The better understanding of the roles of tissues in parasite biology, especially in development, reproduction and interactions with its human hosts, should promote future investigations into pathogenesis and control of these significant parasites. [ABSTRACT FROM AUTHOR]

Background: The functions of many schistosome gene products remain to be characterized. A major step towards elucidating function of these genes would be in defining their sites of expression. This goal is rendered difficult to achieve by the generally small size of the parasites and the lack of a body cavity, which precludes analysis of transcriptional profiles of the tissues in isolation. Methodology/Principal Findings: Here, we describe a combined laser microdissection microscopy (LMM) and microarray analysis approach to expedite tissue specific profiling and gene atlasing for tissues of adult female Schistosoma japonicum. This approach helps to solve the gene characterization ''bottle-neck'' brought about by acoelomy and the size of these parasites. Complementary RNA obtained after isolation from gastrodermis (parasite gut mucosa), vitelline glands and ovary by LMM were subjected to microarray analyses, resulting in identification of 147 genes upregulated in the gastrodermis, 4,149 genes in the ovary and 2,553 in the vitellaria. Conclusions: This work will help to shed light on the molecular pathobiology of this debilitating human parasite and aid in the discovery of new targets for the development of anti-schistosome vaccines and drugs. [ABSTRACT FROM AUTHOR]

Background: The schistosome blood flukes are complex trematodes and cause a chronic parasitic disease of significant public health importance worldwide, schistosomiasis. Their life cycle is characterised by distinct parasitic and free-living phases involving mammalian and snail hosts and freshwater. Microarray analysis was used to profile developmental gene expression in the Asian species, Schistosoma japonicum. Total RNAs were isolated from the three distinct environmental phases of the lifecycle - aquatic/snail (eggs, miracidia, sporocysts, cercariae), juvenile (lung schistosomula and paired but pre-egg laying adults) and adult (paired, mature males and eggproducing females, both examined separately). Advanced analyses including ANOVA, principal component analysis, and hierarchal clustering provided a global synopsis of gene expression relationships among the different developmental stages of the schistosome parasite. Results: Gene expression profiles were linked to the major environmental settings through which the developmental stages of the fluke have to adapt during the course of its life cycle. Gene ontologies of the differentially expressed genes revealed a wide range of functions and processes. In addition, stage-specific, differentially expressed genes were identified that were involved in numerous biological pathways and functions including calcium signalling, sphingolipid metabolism and parasite defence. Conclusion: The findings provide a comprehensive database of gene expression in an important human pathogen, including transcriptional changes in genes involved in evasion of the host immune response, nutrient acquisition, energy production, calcium signalling, sphingolipid metabolism, egg production and tegumental function during development. This resource should help facilitate the identification and prioritization of new anti-schistosome drug and vaccine targets for the control of schistosomiasis. [ABSTRACT FROM AUTHOR]