Schistosomiasis is a devastating neglected tropical disease caused by the parasitic flatworm Schistosoma mansoni. S. mansoni is related to highly regenerative free-living flatworms called planarians. The planarians' regenerative abilities rely upon a pluripotent population of stem cells known as ?neoblasts?. Recent work has described a population of stem cells found in S. mansoni that resembles the neoblasts found within planarians. In schistosomes, these stem cells give rise to a population of progenitor cells which are ultimately responsible for generating the epithelium-like tegument of the parasite. The tegument is widely thought to be a key virulence factor contributing to the schistosome's success as a parasite. I hypothesize that the differentiation of schistosome stem cells into the tegumental lineage is required for maintenance of the tegument and thus contributes to the parasite's virulence. In this proposal, I will characterize the stem and tegument progenitor cells from S. mansoni in order to better understand the biology that underlies this terrible illness. I have generated transcriptomes from schistosome stem cells and tegumental progenitor cells using fluorescence activated cell sorting in conjunction with RNA sequencing. Using these transcriptomes, I have identified candidate genes that are specifically enriched in the stem and tegument progenitor cells that may play important roles in stem cell maintenance and tegumental differentiation. I will validate that the candidate genes are co-expressed with known stem and progenitor cell markers using whole-mount in situ hybridization. Loss- of-function screening using RNAi will enable detection of functional defects in stem cell maintenance and tegumental differentiation. Finally, I hypothesize that perturbing candidate genes that appear to have a critical role in regulating stem cell proliferation or tegument differentiation will result in structural deficits in the tegument. I will test this hypothesis by examining the microscopic structure of the tegument using fluorescence and electron microscopy. Ultimately, these endeavors will further our understanding of the basic biology of the schistosome by describing how schistosome stem cells proliferate and differentiate. Improved understanding in these areas can help identify novel drug targets which can aid in the treatment of this global health burden.
Schistosomiasis is a devastating tropical disease caused by parasitic flatworms known as schistosomes. The worms can survive inside of an infected person for several decades, causing debilitating disease the entire time. We hypothesize that a population of stem cells inside of the worm are responsible for the worm's ability to survive inside the host and that these stem cells represent a new potential drug target.
