Adult somatic stem cells in the human parasite Schistosoma mansoni

Abstract

SummarySchistosomiasis is among the most prevalent human parasitic diseases, affecting more than 200 million people worldwide1. The etiological 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 (e.g., 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 RNAseq-based gene expression profiling, we find that these schistosome neoblast-like cells express a fibroblast growth factor receptor ortholog. Using RNA interference we demonstrate that this gene is required for the maintenance of these neoblast-like cells. Our observations suggest that adaptation of developmental strategies shared by free-living ancestors to modern-day schistosomes likely 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.

Lactate as a Novel Quantitative Measure of Viability in Schistosoma mansoni Drug Sensitivity Assays

“…An additional concern is the reliability of morphological/motility changes reflecting parasite viability. It is known that adult schistosomes can recover damaged tegument after sublethal PZQ doses, and recent investigations have identified somatic stem cells in Schistosoma which show potential for tissue regeneration (17,18).…”

“…To overcome the subjectivity and complexity of microscopy, several novel techniques to determine schistosomulum viability have recently been presented, although microscopy is still the standard reference methodology (12,13,15,16). However, the phenotype and the degree of changes in the worms' morphology and motility heavily depend on the chemical nature of the drug, and in adult worms it has been shown that damaged tissues have the potential to regenerate (17,18). Whether these observations always truly reflect parasite death can only be supposed.…”

Halting harmful helminths

“…Attention has focused on stem cells (also called germinative cells or neoblasts) and the tissues in which they reside because these cells self-replicate as well as differentiate and, hence, endow the evolutionary and developmental plasticity of parasitic flatworms. It is now feasible to isolate gonads enriched in stem cells ( 8), identify somatic proliferating stem cells ( 9), and initiate limited-passage cell cultures from schistosomes ( 14). Also promising are advances in cell cultivation systems for echinococcal tapeworms, where continuous cultures enriched for replicative and differentiating stem cells can be derived from Echinococcus multilocularis ( 10) and "immortal" cell lines can be produced from the closely related species E. granulosus ( 11).…”

“…Despite these hurdles, progress in the areas of schistosome (blood fluke) transgenesis ( 7), organ isolation ( 8), and stem cell characterization ( 9), coupled with advances in echinococcal (hydatid tapeworm) primary cell cultures ( 10,11), portends a transformation in the ability to manipulate and study parasitic flatworms. As a prelude to whole organism or cellular transgenesis, techniques have been honed over the past 15 years to perform loss-of-function studies in schistosomes using posttranscriptional gene silencing ( 12).…”

Preliminary characterization and expression of Vasa-like gene in Schistosoma japonicum

“…Little information on the transcription and translation profile of the Vasa gene in S. japonicum exists, although some reports showed that Vasa homologues in Schistosoma mansoni (S. mansoni), named Smvlg1, Smvlg2, and Smvlg3, are transcribed in the posterior ovary (Skinner et al 2012). Furthermore, Vasa, Piwi, Tudor, Tsunagi, and Nanos genes represent potential regulators of proliferating somatic cell (PSC) behavior and could serve as useful markers for these cells in human parasites (Collins et al 2013;Liu et al 2010). …”