Abstract
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.
Highlights
Schistosomes are parasitic flatworms causing one of the most prevalent infectious diseases from which millions of people are currently suffering
Through RNA interference (RNAi) mediated gene knockdown, we evaluate the function of germline stem cells (GSCs)-enriched transcripts and find that a schistosome homolog of onecut homeobox transcription factor, onecut-1, is the key regulator that balances the proliferation and differentiation of GSCs. onecut-1 functions through complex epistatic interactions with several other genes, including eled, nanos, and boule
We found that boule expression was undetectable after oc-1 RNAi, and oc-1 expression was eliminated upon boule RNAi (Fig. 5a)
Summary
Schistosomes are parasitic flatworms causing one of the most prevalent infectious diseases from which millions of people are currently suffering. While our previous work has identified the origin of the schistosome germline, it remains unclear which molecular regulatory program(s) underlies the separation of somatic and germ cell lineages[5] In contrast to their distinct cellular fates, somatic and germline stem cells share strikingly similar gene expression signatures, including genes involved in regulating the cell cycle, a set of conserved RNA binding proteins that are often associated with stem cell multipotency[4,5,6], and transcription factors such as nuclear factor Y subunits[18]. Planarian germline stem cells resemble their somatic stem cells both in terms of morphology and molecular signatures, and can even contribute to somatic tissues during tissue regeneration after injury[20,21,22,23,24]
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