Biology subjects

Wendt, G. R.

Publications and source records attributed to Wendt, G. R..

3 recordsLinked to original sources

bioRxiv2024

A Kruppel-like factor establishes cellular heterogeneity during schistosome tegumental maintenance

Schistosomes are blood-dwelling parasitic flatworms that rely on a syncytial surface coat, known as the tegument, for long-term survival and immune evasion in the blood of their human hosts. Previous studies have shown that cells within the tegumental syncytium are perpetually turned over and renewed by somatic stem cells called neoblasts. Yet, little is known about this renewal process on a molecular level. Here, we characterized a Kruppel-like factor 4 (klf4) using a combination of bulk and single cell RNAseq approaches and demonstrate that klf4 is essential for the maintenance of a specific tegumental lineage, resulting in the loss of a subpopulation of molecularly-unique tegument cells. Thus, klf4 is critical for maintaining the balance between different tegumental progenitor pools, thereby fine-tuning the molecular composition of the mature tegument. Understanding these distinct tegumental cell populations is expected to provide insights into parasite defense mechanisms and suggest new avenues for therapeutics.

microbiology↗

bioRxiv2024

Horizontal gene transfer of a functional cki homolog in the human pathogen Schistosoma mansoni

Schistosomes, parasitic flatworms responsible for the neglected tropical disease schistosomiasis, are protected by a skin-like tegument, and tegument maintenance is controlled by a schistosome ortholog (p53-1) of the tumor suppressor TP53. To understand p53-1 function, we characterized a schistosome cyclin dependent kinase inhibitor homolog (cki). Knockdown of cki resulted in hyperproliferation, that, combined with p53-1 knockdown yielded tumor-like growths, indicating that cki and p53-1 are tumor suppressors in Schistosoma mansoni. Interestingly, cki homologs are ubiquitous in parasitic flatworms but are absent from their free-living ancestors, suggesting cki may have come from horizontal gene transfer. This suggests that the evolution of parasitism in flatworms was aided by an unusual means of metazoan genetic inheritance. TeaserHorizontal gene transfer may have played an important role in the evolution of parasitic flatworms

microbiology↗

bioRxiv2021

Convergent evolution of genome guardian functions in a parasite-specific p53 homolog

SignificanceP53 is a widely studied tumor suppressor that is found throughout metazoans, including invertebrates that do not develop malignancies. The prevailing theory for why this is the case is that P53 originally evolved to protect the germline of early metazoans from genotoxic stress such as UV radiation. In this study, we examine the function of two P53 homologs in the parasitic flatworm Schistosoma mansoni. The first is orthologous to canonical P53, and regulates stem cell maintenance and differentiation. The second P53 gene is a parasite-specific paralog that is required for the normal response to genotoxic stress. This implies that the ability to respond to genotoxic stress in parasitic flatworms may have arisen from convergent evolution.

evolutionary biology↗