Comparative analysis of Wnt expression identifies a highly conserved developmental transition in flatworms

Koziol, Uriel; Jarero, Francesca; Olson, Peter D.; Brehm, Klaus

doi:10.1186/s12915-016-0233-x

Cited by 52 publications

(106 citation statements)

References 79 publications

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“…Similar to what has been observed in planarians 18 , tapeworms 19 , and acoels 20 , we find that many well-characterized morphogens that regulate wnt (Extended Data Fig 4a-d) and tgfb signaling (Extended Data Fig. 4e-h) are predominantly expressed in muscle and neuronal cells.…”

Section: Figsupporting

confidence: 84%

A single-cell RNAseq atlas of the pathogenic stage ofSchistosoma mansoniidentifies a key regulator of blood feeding

Wendt

Zhao

Chen

et al. 2020

Preprint

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Schistosomiasis is an ancient and chronic neglected tropical disease that infects over 240 million people and kills over 200,000 of the world’s poorest people every year1, 2. There are no vaccines and because there is only one drug available, the need for new therapeutics is great. The causative agents of this disease are flatworm parasites that dwell inside the host’s circulation, often for decades, where they feed on blood and lay eggs which are primarily responsible for disease pathology. As metazoans comprised of multiple tissue types, understanding the schistosome’s tissues on a molecular level and their functions during what can be decades of successful parasitism could suggest novel therapeutic strategies. Here, we employ single-cell RNAseq to characterize 43,642 cells from the pathogenic (adult) stage of the schistosome lifecycle. From these data, we characterize 68 molecularly distinct cell populations that comprise nearly all tissues described morphologically, including the nervous and reproductive systems. We further uncover a lineage of somatic stem cells responsible for producing and maintaining the parasite’s gut – the primary tissue responsible for digestion of host blood. Finally, we show that a homologue of hepatocyte nuclear factor 4 (hnf4) is expressed in this gut lineage and required for gut maintenance, blood feeding and inducing egg-associated pathology in vivo. Together, the data highlight the utility of this single-cell RNAseq atlas to understand schistosome biology and identify potential therapeutic interventions.

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Section: Figsupporting

confidence: 84%

A single-cell RNAseq atlas of the pathogenic stage ofSchistosoma mansoniidentifies a key regulator of blood feeding

Wendt

Zhao

Chen

et al. 2020

Preprint

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“…As a direct result of the unveiling of the complete genomes of the Echinococcus spp., several metabolic pathways have been explored, and other inhibitors are currently being studied (177,(282)(283)(284)(285)(286)(287). Nilotinib, an ABL (Abelson murine leukemia viral oncogene homologue)-tyrosine kinase inhibitor, and everolimus, a serine/threonine kinase inhibitor, caused alterations of E. multilocularis metacestode vesicles in vitro; however, neither of these compounds resulted in any reduction of parasite growth in E. multilocularis-infected mice, and combined application of the kinase inhibitors with ABZ did not lead to synergistic or additive treatment efficacy (282).…”

Section: Improving Diagnosis and Drug Treatment Of Echinococcosismentioning

confidence: 99%

Echinococcosis: Advances in the 21st Century

Wen¹,

Vuitton²,

et al. 2019

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SUMMARY Echinococcosis is a zoonosis caused by cestodes of the genus Echinococcus (family Taeniidae). This serious and near-cosmopolitan disease continues to be a significant public health issue, with western China being the area of highest endemicity for both the cystic (CE) and alveolar (AE) forms of echinococcosis. Considerable advances have been made in the 21st century on the genetics, genomics, and molecular epidemiology of the causative parasites, on diagnostic tools, and on treatment techniques and control strategies, including the development and deployment of vaccines. In terms of surgery, new procedures have superseded traditional techniques, and total cystectomy in CE, ex vivo resection with autotransplantation in AE, and percutaneous and perendoscopic procedures in both diseases have improved treatment efficacy and the quality of life of patients. In this review, we summarize recent progress on the biology, epidemiology, diagnosis, management, control, and prevention of CE and AE. Currently there is no alternative drug to albendazole to treat echinococcosis, and new compounds are required urgently. Recently acquired genomic and proteomic information can provide a platform for improving diagnosis and for finding new drug and vaccine targets, with direct impact in the future on the control of echinococcosis, which continues to be a global challenge.

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“…This evolutionarily conserved pathway regulates crucial aspects of cell fate determination, cell migration, cell polarity, neural patterning and organogenesis in metazoan embryonic development [50]. E. multilocularis and other flatworms possess genes associated with each of the three known Wnt pathways [51,52], and recently Koziol et al [53] showed that the Wnt pathway is involved in anterior-posterior specification in E. multilocularis larvae. In concordance with our results, this signalling pathway has recently also been shown to be regulated by miRNAs in the platyhleminth S. japonicum [22].…”

Section: Gene Id Annotationmentioning

confidence: 99%

Deciphering the role of miR-71 in Echinococcus multilocularis early development in vitro

et al. 2019

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Echinococcosis represents a major public health problem worldwide and is considered a neglected disease by the World Health Organization. The etiological agents are Echinococcus tapeworms, which display elaborate developmental traits that imply a complex control of gene expression. MicroRNAs (miRNAs), a class of small regulatory RNAs, are involved in the regulation of many biological processes such as development and metabolism. They act through the repression of messenger RNAs (mRNAs) usually by binding to the 3' untranslated region (3'UTR). Previously, we described the miRNome of several Echinococcus species and found that miRNAs are highly expressed in all life cycle stages, suggesting an important role in gene expression regulation. However, studying the role of miRNAs in helminth biology remains a challenge. To develop methodology for functional analysis of miR-NAs in tapeworms, we performed miRNA knockdown experiments in primary cell cultures of Echinococcus multilocularis, which mimic the development of metacestode vesicles from parasite stem cells in vitro. First, we analysed the miRNA repertoire of E. multilocularis primary cells by small RNA-seq and found that miR-71, a bilaterian miRNA absent in vertebrate hosts, is one of the top five most expressed miRNAs. Using genomic information and bioinformatic algorithms for miRNA binding prediction, we found a high number of potential miR-71 targets in E. multilocularis. Inhibition of miRNAs can be achieved by transfection of antisense oligonucleotides (anti-miRs) that block miRNA function. To this end, we evaluated a variety of chemically modified anti-miRs for miR-71 knockdown. Electroporation of primary cells with 2'-O-methyl modified anti-miR-71 led to significantly reduced miR-71 levels. Transcriptomic analyses showed that several predicted miR-71 targets were up-regulated in anti-miR-treated primary cells, including genes potentially involved in parasite development, host parasite interaction, and several genes of as yet unknown function. Notably, miR-71silenced primary cell cultures showed a strikingly different phenotype from control cells and did not develop into fully mature metacestodes. These findings indicate an important function of miR-71 in Echinococcus development and provide, for the first time, methodology to functionally study miRNAs in a tapeworm.

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Comparative analysis of Wnt expression identifies a highly conserved developmental transition in flatworms

Cited by 52 publications

References 79 publications

A single-cell RNAseq atlas of the pathogenic stage ofSchistosoma mansoniidentifies a key regulator of blood feeding

A single-cell RNAseq atlas of the pathogenic stage ofSchistosoma mansoniidentifies a key regulator of blood feeding

Echinococcosis: Advances in the 21st Century

Deciphering the role of miR-71 in Echinococcus multilocularis early development in vitro

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