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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 worldwide1. 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 decades2, 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 flatworms3,4 (for example, planarians), and neoblast-like cells have been described in some parasitic tapeworms5, 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 resources6,7 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.

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Figure 1: Proliferation of somatic cells in adult schistosomes.
Figure 2: Transcriptional profiling identifies genes expressed in proliferative cells.
Figure 3: PSCs self-renew and differentiate.
Figure 4: SmfgfrA is required for the maintenance of somatic stem cells.

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Gene Expression Omnibus

Data deposits

RNA-seq analyses have been deposited in the NCBI Gene Expression Omnibus under accession number GSE42757.

References

  1. Chitsulo, L., Engels, D., Montresor, A. & Savioli, L. The global status of schistosomiasis and its control. Acta Trop. 77, 41–51 (2000)

    Article  CAS  Google Scholar 

  2. Basch, P. F. Schistosomes: Development, Reproduction, and Host Relations (Oxford Univ. Press, 1991)

    Google Scholar 

  3. Wagner, D. E., Wang, I. E. & Reddien, P. W. Clonogenic neoblasts are pluripotent adult stem cells that underlie planarian regeneration. Science 332, 811–816 (2011)

    Article  CAS  ADS  Google Scholar 

  4. Newmark, P. A. & Sánchez Alvarado, A. Not your father’s planarian: a classic model enters the era of functional genomics. Nature Rev. Genet. 3, 210–219 (2002)

    Article  CAS  Google Scholar 

  5. Brehm, K. Echinococcus multilocularis as an experimental model in stem cell research and molecular host-parasite interaction. Parasitology 137, 537–555 (2010)

    Article  CAS  Google Scholar 

  6. Protasio, A. V. et al. A systematically improved high quality genome and transcriptome of the human blood fluke Schistosoma mansoni. PLoS Negl. Trop. Dis. 6, e1455 (2012)

    Article  CAS  Google Scholar 

  7. Berriman, M. et al. The genome of the blood fluke Schistosoma mansoni. Nature 460, 352–358 (2009)

    Article  CAS  ADS  Google Scholar 

  8. Den Hollander, J. E. & Erasmus, D. A. Schistosoma mansoni: DNA synthesis in males and females from mixed and single-sex infections. Parasitology 88, 463–476 (1984)

    Article  CAS  Google Scholar 

  9. Nollen, P. M., Floyd, R. D., Kolzow, R. G. & Deter, D. L. The timing of reproductive cell development and movement in Schistosoma mansoni, S. japonicum, and S. haematobium, using techniques of autoradiography and transplantation. J. Parasitol. 62, 227–231 (1976)

    Article  CAS  Google Scholar 

  10. Salic, A. & Mitchison, T. J. A chemical method for fast and sensitive detection of DNA synthesis in vivo. Proc. Natl Acad. Sci. USA 105, 2415–2420 (2008)

    Article  CAS  ADS  Google Scholar 

  11. Newmark, P. A. & Sánchez Alvarado, A. Bromodeoxyuridine specifically labels the regenerative stem cells of planarians. Dev. Biol. 220, 142–153 (2000)

    Article  CAS  Google Scholar 

  12. Forsthoefel, D. J., Park, A. E. & Newmark, P. A. Stem cell-based growth, regeneration, and remodeling of the planarian intestine. Dev. Biol. 356, 445–459 (2011)

    Article  CAS  Google Scholar 

  13. Baguñá, J. & Romero, R. Quantitative analysis of cell types during growth, degrowth and regeneration in the planarians Dugesia mediterranea and Dugesia tigrina. Hydrobiologia 84, 181–194 (1981)

    Article  Google Scholar 

  14. Wagner, D. E., Ho, J. J. & Reddien, P. W. Genetic regulators of a pluripotent adult stem cell system in planarians identified by RNAi and clonal analysis. Cell Stem Cell 10, 299–311 (2012)

    Article  CAS  Google Scholar 

  15. Solana, J. et al. Defining the molecular profile of planarian pluripotent stem cells using a combinatorial RNAseq, RNA interference and irradiation approach. Genome Biol. 13, R19 (2012)

    Article  CAS  Google Scholar 

  16. Eisenhoffer, G. T., Kang, H. & Sánchez Alvarado, A. Molecular analysis of stem cells and their descendants during cell turnover and regeneration in the planarian Schmidtea mediterranea. Cell Stem Cell 3, 327–339 (2008)

    Article  CAS  Google Scholar 

  17. Caffrey, C. R., McKerrow, J. H., Salter, J. P. & Sajid, M. Blood ‘n’ guts: an update on schistosome digestive peptidases. Trends Parasitol. 20, 241–248 (2004)

    Article  CAS  Google Scholar 

  18. Önal, P. et al. Gene expression of pluripotency determinants is conserved between mammalian and planarian stem cells. EMBO J. 31, 2755–2769 (2012)

    Article  Google Scholar 

  19. Labbé, R. M. et al. A comparative transcriptomic analysis reveals conserved features of stem cell pluripotency in planarians and mammals. Stem Cells 30, 1734–1745 (2012)

    Article  Google Scholar 

  20. Pearson, B. J. & Sánchez Alvarado, A. A planarian p53 homolog regulates proliferation and self-renewal in adult stem cell lineages. Development 137, 213–221 (2010)

    Article  CAS  Google Scholar 

  21. Ogawa, K. et al. Planarian fibroblast growth factor receptor homologs expressed in stem cells and cephalic ganglions. Dev. Growth Differ. 44, 191–204 (2002)

    Article  CAS  Google Scholar 

  22. Rouhana, L., Shibata, N., Nishimura, O. & Agata, K. Different requirements for conserved post-transcriptional regulators in planarian regeneration and stem cell maintenance. Dev. Biol. 341, 429–443 (2010)

    Article  CAS  Google Scholar 

  23. Juliano, C. & Wessel, G. Versatile germline genes. Science 329, 640–641 (2010)

    Article  CAS  Google Scholar 

  24. Skinner, D. E. et al. Vasa-like DEAD-box RNA helicases of Schistosoma mansoni. PLoS Negl Trop Dis 6, e1686 (2012)

    Article  CAS  Google Scholar 

  25. Lanner, F. & Rossant, J. The role of FGF/Erk signaling in pluripotent cells. Development 137, 3351–3360 (2010)

    Article  CAS  Google Scholar 

  26. Davies, S. J. et al. Modulation of blood fluke development in the liver by hepatic CD4+ lymphocytes. Science 294, 1358–1361 (2001)

    Article  CAS  ADS  Google Scholar 

  27. Severinghaus, A. E. Sex studies on Schistosoma japonicum. Q. J. Microsc. Sci. 71, 653–702 (1928)

    Google Scholar 

  28. Shaw, M. K. & Erasmus, D. A. Schistosoma mansoni: structural damage and tegumental repair after in vivo treatment with praziquantel. Parasitology 94, 243–254 (1987)

    Article  CAS  Google Scholar 

  29. Collins, J. J., III et al. Genome-wide analyses reveal a role for peptide hormones in planarian germline development. PLoS Biol. 8, e1000509 (2010)

    Article  Google Scholar 

  30. Collins, J. J., III, King, R. S., Cogswell, A., Williams, D. L. & Newmark, P. A. An atlas for Schistosoma mansoni organs and life-cycle stages using cell type-specific markers and confocal microscopy. PLoS Negl. Trop. Dis. 5, e1009 (2011)

    Article  Google Scholar 

  31. Lewis, F. Schistosomiasis. Curr. Protoc. Immunol. Ch. 19, Unit 19 11. (2001)

  32. Basch, P. F. Cultivation of Schistosoma mansoni in vitro. I. Establishment of cultures from cercariae and development until pairing. J. Parasitol. 67, 179–185 (1981)

    Article  CAS  Google Scholar 

  33. Cogswell, A. A., Collins, J. J., III, Newmark, P. A. & Williams, D. L. Whole mount in situ hybridization methodology for Schistosoma mansoni. Mol. Biochem. Parasitol. 178, 46–50 (2011)

    Article  CAS  Google Scholar 

  34. Neef, A. B. & Luedtke, N. W. Dynamic metabolic labeling of DNA in vivo with arabinosyl nucleosides. Proc. Natl Acad. Sci. USA 108, 20404–20409 (2011)

    Article  CAS  ADS  Google Scholar 

  35. Abramoff, M. D., Magelhaes, P. J. & Ram, S. J. Image processing with ImageJ. Biophotonics Int. 11, 36–42 (2004)

    Google Scholar 

  36. Falcon, S. & Gentleman, R. Using GOstats to test gene lists for GO term association. Bioinformatics 23, 257–258 (2007)

    Article  CAS  Google Scholar 

  37. Skelly, P. J., Da’dara, A. & Harn, D. A. Suppression of cathepsin B expression in Schistosoma mansoni by RNA interference. Int. J. Parasitol. 33, 363–369 (2003)

    Article  CAS  Google Scholar 

  38. Boyle, J. P., Wu, X. J., Shoemaker, C. B. & Yoshino, T. P. Using RNA interference to manipulate endogenous gene expression in Schistosoma mansoni sporocysts. Mol. Biochem. Parasitol. 128, 205–215 (2003)

    Article  CAS  Google Scholar 

  39. Štefanić, S. et al. RNA interference in Schistosoma mansoni schistosomula: selectivity, sensitivity and operation for larger-scale screening. PLoS Negl. Trop. Dis. 4, e850 (2010)

    Article  Google Scholar 

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Acknowledgements

We thank R. Roberts-Galbraith, M. Issigonis and L. Rouhana for comments on the manuscript; R. King for sharing the cathepsin B plasmid and unpublished protocols; and A. Hernandez for assistance with Illumina sequencing. Schistosome-infected mice were provided by the NIAID Schistosomiasis Resource Center and the Biomedical Research Institute through NIAID contract no. HHSN272201000005I. This work was supported by: NIH F32 HD062124 (J.J.C.) and NIH R21 AI099642 (P.A.N.). P.A.N. is an investigator of the Howard Hughes Medical Institute.

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J.J.C., B.W., B.G.L., M.E.T. and H.I. performed experiments. J.J.C. and B.W. analysed data. J.J.C. and P.A.N. designed the study and wrote the paper.

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Correspondence to Phillip A. Newmark.

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The authors declare no competing financial interests.

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This file contains Supplementary Figures 1-9, a Supplementary Discussion, Supplementary Tables 2-3 and Supplementary References. (PDF 1610 kb)

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Collins III, J., Wang, B., Lambrus, B. et al. Adult somatic stem cells in the human parasite Schistosoma mansoni . Nature 494, 476–479 (2013). https://doi.org/10.1038/nature11924

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