Systematically improved in vitro culture conditions reveal new insights into the reproductive biology of the human parasite Schistosoma mansoni

Wang, Jipeng; Chen, Rui; Collins, James J.

doi:10.1371/journal.pbio.3000254

Cited by 78 publications

(90 citation statements)

References 56 publications

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“…We also identified two clearly distinguishable subclusters marked by boule (Smp_144860) and a nuclear receptor ( nr , Smp_248100), respectively. As nr is known to be expressed in the nanos-1 + stem cells (also known as S1 cells) in primordial vitellaria 47 , 48 , a yolk cell-producing somatic reproductive organ in female schistosomes, these observations suggest that the nanos-1 + cluster contains two transcriptionally similar but distinct cell types: S1 cells ( nr + ) and GSCs ( boule + ).…”

Section: Resultsmentioning

confidence: 91%

Single-cell analysis of Schistosoma mansoni identifies a conserved genetic program controlling germline stem cell fate

Sarfati

Xue

et al. 2021

Nat Commun

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Schistosomes are parasitic flatworms causing one of the most prevalent infectious diseases from which millions of people are currently suffering. These parasites have high fecundity and their eggs are both the transmissible agents and the cause of the infection-associated pathology. Given its biomedical significance, the schistosome germline has been a research focus for more than a century. Nonetheless, molecular mechanisms that regulate its development are only now being understood. In particular, it is unknown what balances the fate of germline stem cells (GSCs) in producing daughter stem cells through mitotic divisions versus gametes through meiosis. Here, we perform single-cell RNA sequencing on juvenile schistosomes and capture GSCs during de novo gonadal development. We identify a genetic program that controls the proliferation and differentiation of GSCs. This program centers around onecut, a homeobox transcription factor, and boule, an mRNA binding protein. Their expressions are mutually dependent in the schistosome male germline, and knocking down either of them causes over-proliferation of GSCs and blocks germ cell differentiation. We further show that this germline-specific regulatory program is conserved in the planarian, schistosome’s free-living evolutionary cousin, but the function of onecut has changed during evolution to support GSC maintenance.

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Section: Resultsmentioning

confidence: 91%

Single-cell analysis of Schistosoma mansoni identifies a conserved genetic program controlling germline stem cell fate

Sarfati

Xue

et al. 2021

Nat Commun

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“…1a). Schistosomes are unique among flatworms in that they are dioecious 9 and sexual maturation of the female worm’s reproductive organs, including the ovary and vitellaria, requires close and sustained physical contact with the male worm 10 . Accordingly, to create a single cell atlas with the greatest diversity of cell types, we generated scRNAseq libraries from adult male parasites, adult sexually-mature female parasites, and age-matched virgin female parasites.…”

Section: Figmentioning

confidence: 99%

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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“…Classical studies of cell proliferation in blood flukes have focused on the reproductive system of adult worms ( 38 ), given the critical dual role of eggs in schistosome transmission and in the immunopathology induced by ova trapped in host tissues. Uniquely amongst the Platyhelminthes, female adult schistosomes live partially enclosed within a specialized gynaecophoric canal on the ventral surface of the male worm's body; the growth and sexual maturity of female worms are heavily reliant on continuous pairing with male worms to fuel the maturation of their reproductive organs ( 39 ). Maturation of the vitellaria, which produce cells that form egg shells and are packaged into the egg with the zygote, is highly dependent on the presence of the male.…”

Section: The Key Roles Played By Stem Cells Throughout the Schistosommentioning

confidence: 99%

Innovations and Advances in Schistosome Stem Cell Research

et al. 2021

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Schistosomes infect about 250 million people globally causing the devastating and persistent disease of schistosomiasis. These blood flukes have a complicated life cycle involving alternating infection of freshwater snail intermediate and definitive mammalian hosts. To survive and flourish in these diverse environments, schistosomes transition through a number of distinct life-cycle stages as a result of which they change their body plan in order to quickly adapt to each new environment. Current research suggests that stem cells, present in adults and larvae, are key in aiding schistosomes to facilitate these changes. Given the recent advances in our understanding of schistosome stem cell biology, we review the key roles that two major classes of cells play in the different life cycle stages during intramolluscan and intramammalian development; these include the germinal cells of sporocysts involved in asexual reproduction in molluscan hosts and the neoblasts of adult worms involved in sexual reproduction in human and other mammalian hosts. These studies shed considerable new light in revealing the stem cell heterogeneity driving the propagation of the schistosome life cycle. We also consider the possibility and value of establishing stem cell lines in schistosomes to advance schistosomiasis research. The availability of such self-renewable resources will provide new platforms to study stem cell behavior and regulation, and to address fundamental aspects of schistosome biology, reproductive development and survival. In turn, such studies will create new avenues to unravel individual gene function and to optimize genome-editing processes in blood flukes, which may lead to the design of novel intervention strategies for schistosomiasis.

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Systematically improved in vitro culture conditions reveal new insights into the reproductive biology of the human parasite Schistosoma mansoni

Cited by 78 publications

References 56 publications

Single-cell analysis of Schistosoma mansoni identifies a conserved genetic program controlling germline stem cell fate

Single-cell analysis of Schistosoma mansoni identifies a conserved genetic program controlling germline stem cell fate

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

Innovations and Advances in Schistosome Stem Cell Research

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