Adult somatic stem cells in the human parasite Schistosoma mansoni
ABSTRACT Schistosomiasis is among the most prevalent human parasitic diseases, affecting more than 200 million people worldwide. The aetiological agents of this disease are trematode flatworms (Schistosoma) that live and lay eggs within the vasculature of the host. These eggs lodge in host tissues, causing inflammatory responses that are the primary cause of morbidity. Because these parasites can live and reproduce within human hosts for decades, elucidating the mechanisms that promote their longevity is of fundamental importance. Although adult pluripotent stem cells, called neoblasts, drive long-term homeostatic tissue maintenance in long-lived free-living flatworms (for example, planarians), and neoblast-like cells have been described in some parasitic tapeworms, little is known about whether similar cell types exist in any trematode species. Here we describe a population of neoblast-like cells in the trematode Schistosoma mansoni. These cells resemble planarian neoblasts morphologically and share their ability to proliferate and differentiate into derivatives of multiple germ layers. Capitalizing on available genomic resources and RNA-seq-based gene expression profiling, we find that these schistosome neoblast-like cells express a fibroblast growth factor receptor orthologue. Using RNA interference we demonstrate that this gene is required for the maintenance of these neoblast-like cells. Our observations indicate that adaptation of developmental strategies shared by free-living ancestors to modern-day schistosomes probably contributed to the success of these animals as long-lived obligate parasites. We expect that future studies deciphering the function of these neoblast-like cells will have important implications for understanding the biology of these devastating parasites.
SourceAvailable from: Eduardo E Zattara[Show abstract] [Hide abstract]
ABSTRACT: Animals differ markedly in their ability to regenerate, yet still little is known about how regeneration evolves. In recent years, important advances have been made in our understanding of animal phylogeny and these provide new insights into the phylogenetic distribution of regeneration. The developmental basis of regeneration is also being investigated in an increasing number of groups, allowing commonalities and differences across groups to become evident. Here, we focus on regeneration in the Spiralia, a group that includes several champions of animal regeneration, as well as many groups with more limited abilities. We review the phylogenetic distribution and developmental processes of regeneration in four major spiralian groups: annelids, nemerteans, platyhelminths, and molluscs. Although comparative data are still limited, this review highlights phylogenetic and developmental patterns that are emerging regarding regeneration in spiralians and identifies important avenues for future research.The International Journal of Developmental Biology 12/2014; 58:623 - 634. DOI:10.1387/ijdb.140142ab · 2.57 Impact Factor
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ABSTRACT: Whole-organism compound sensitivity assays are a valuable strategy in infectious diseases to identify active molecules. In schistosomiasis drug discovery, larval stage Schistosoma allows a certain degree of automation in screening of compounds. Unfortunately throughput is limited as drug activity is determined by manual assessment of Schistosoma viability by microscopy. To develop a simple and quantifiable surrogate marker for viability, we targeted glucose metabolism which is central to Schistosoma survival. Lactate is the end-product of glycolysis in human Schistosoma stages and can be detected in the supernatant. We assessed lactate as a surrogate marker for viability in Schistosoma drug screening assays. We thoroughly investigated parameters of lactate measurement and performed drug sensitivity assays applying schistosomula and adult worms for proof of concept. Lactate levels clearly reflected viability of schistosomula and correlated with schistosomula numbers. Compounds with reported potencies were tested and activities were determined by lactate assay and by microscopy. We conclude that lactate is a sensitive and simple to measure surrogate marker for Schistosoma viability in compound screening assays. Low numbers of schistosomula and commercial availability of lactate assay reagents make the assay particularly attractive to throughput approaches. Furthermore, standardization of procedures and quantitative evaluation of compound activities facilitate inter-assay comparison of potencies and thus concerted drug discovery approaches. Copyright © 2014, American Society for Microbiology. All Rights Reserved.Antimicrobial Agents and Chemotherapy 12/2014; DOI:10.1128/AAC.03809-14 · 4.45 Impact Factor
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ABSTRACT: Efficient synthesis of 5-[3,6-di(pyridin-2-yl)pyridazine-4-yl]-2′-deoxyuridine-5′-O-triphosphate, a potential substrate for fluorescence detection and imaging of DNA is reported. Inverse electron demand Diels–Alder (invDA) reaction between the electron-rich 5-vinyl-2′-deoxyuridine-5′-O-triphosphate and electron-deficient tetrazine dienophile 3,6-di(pyridin-2-yl)-1,2,4,5-tetrazine resulted in the formation of 5-[3,6-di(pyridin-2-yl)pyridazine-4-yl]-2′-deoxyuridine-5′-O-triphosphate in 80% yield. This class of molecules will find applications in polymerase chain reactions for fluorescence detection and imaging applications of cellular DNA.Tetrahedron Letters 02/2015; DOI:10.1016/j.tetlet.2014.12.100 · 2.39 Impact Factor