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Kershenbaum, S.

Publications and source records attributed to Kershenbaum, S..

3 recordsLinked to original sources

Cell atlases of schistosome human infective stages reveal larval tissue fates and innovations

Schistosomes infect over 250 million people, yet the cellular basis of their human-infective cercaria larva, that drives transmission and infection, remains poorly understood. We present single-cell atlases of Schistosoma mansoni cercariae, widely regarded as transcriptionally quiescent, and schistosomula, the first intra-mammalian stage. Twenty-two cercarial cell types either persist into schistosomula or are lost. The tail harbours several cercaria-specific innovations, including a novel tegument. Gene-age analysis supports the cercaria as the most recent addition to the life cycle and tail cells as younger than body cells. Persisting cell types undergo clear transcriptional transitions which give new insights into the dynamics of cercarial transformation into schistosomula. These findings link the recent origin of cercarial cell types to the evolution of active dispersal and transmission in digenean parasites.

genomics↗

In vitro sexual dimorphism establishment in schistosomes

Schistosomes are parasitic flatworms that cause Schistosomiasis, a major Neglected Tropical Disease (NTD) that affects more than 250 million people worldwide. With two morphologically distinct sexes, a heterogametic female (ZW) and a homogametic male (ZZ), schistosomes are an exception among flatworms, which are largely hermaphroditic. Sexual dimorphism in schistosomes only becomes apparent by adulthood within the mammalian host. The cellular and molecular mechanisms underlying the sexual differentiation of these parasites are poorly understood, partly due to intrinsic challenges in assessing parasite development in vivo. Therefore, robust and reproducible approaches for maintaining and developing parasites in vitro are needed to overcome these difficulties. However, to date, only a few studies have focused on protocols that allow cultured parasites to reach sexual dimorphic stages, and none have been reproduced, limiting the ability to understand the unique sexual biology of this major human parasite. Here, we refine a protocol for long-term culture of newly transformed cercariae that developed in vitro into sexually dimorphic forms. We assessed the effect of two different sera, Foetal Bovine Serum (FBS) and Human Serum (HS), added to the culture medium supplemented with human red blood cells. We found that in contrast to FBS-cultured worms, HS-cultured parasites digested red blood cells, a crucial step for long term parasite development. Additionally, while most FBS-cultured parasites did not progress beyond an early liver stage, sexual dimorphism was clearly established in the HS-cultured worms, albeit delayed compared to in vivo development. Moreover, EdU pulse experiments revealed a continuous proliferation of cells over time in HS-cultured parasites, while a significantly lower number of proliferating cells were detected in FBS-cultured worms. This protocol paves the way to study parasite development in vitro, positively impacting the principles of the 3Rs (Replacement, Reduction and Refinement) for animal research, and allowing for in-depth studies of sexual dimorphism establishment as well as in vitro screening for novel control strategies across the life cycle of these major human parasites.

developmental biology↗

Gene conversion limits the cost of asexuality in immortal worms

Most multicellular organisms reproduce sexually despite the costs associated with sexuality. This has been explained as the result of selection favouring the ability to recombine the genome. The lack of recombination in asexual species constrains their adaptability and leads to the accumulation of deleterious mutations, ultimately increasing their risk of extinction. Nonetheless, successful asexual life histories persist among multicellular organisms, and explanatory mechanisms which may help limit the cost of asexuality remain enigmatic. In search of these mechanisms, we looked at that the molecular evolutionary changes in the sexual and obligately asexual strains of the planarian flatworm, Schmidtea mediterranea. We find that the accumulation of deleterious mutations in highly conserved genes is largely avoided in the asexual strain. We find evidence that this is achieved by somatic gene conversion in stem cells allowing for the restoration of beneficial alleles and purification of deleterious mutations. Taken together, our analysis identifies gene conversion as a mechanism which may contribute to the maintenance of asexuality in an obligately fissiparous metazoan.

evolutionary biology↗