Characterization of conserved post-transcriptional mechanisms regulating stem cells in planarians and mice

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Pluripotency describes the potential of a cell to give rise to all cell types of an organism. It has been mainly studied in cultured cells derived from embryonic tissues or from somatic cells through iPS technology. However, these cells are deprived of their natural environment and lack important interactions within a stem cell niche through extracellular molecules. In the presented study, we aim to identify and investigate conserved regulatory networks and mechanisms that control stem cell behaviour in vivo. We will use the stem cell systems of two model organisms, planarian adult stem cells and mouse male germline stem cells, which share remarkable features of developmental pluripotency and regenerative power. With the two experimental systems we will be able to go beyond commonly used in vitro culture systems and use planarians and mice as in vivo Petri dishes for research on pluripotent stem cells. Given that posttranscriptional mechanisms for regulating stem cells have been largely neglected, we will establish these processes as crucial players in the control of pluripotency. Using bioinformatics analyses of previous expression data, genes encoding proteins with putative RNA binding motifs and their potential regulatory networks will be identified. Taking advantage of fast and efficient gene silencing by RNA interference (RNAi) in planarians and the recently developed CRISPR/Cas9 gene editing system in mouse, conserved RNA regulating genes will be analyzed for their functions and interaction partners in planarian adult stem cells and mouse spermatogonial stem cells (SSCs). Our study will provide important insights into post-transcriptional mechanisms that control self-renewal versus differentiation of adult stem cells and provide bases for their biomedical exploitation for enhancing tissue regeneration and treating male infertility.