Polyploidy dynamics & interactions across mammalian tissues

Most cells in our bodies are diploid, meaning they carry two copies of each chromosome one from each parent. Sometimes, cells can undergo whole genome duplication, meaning they end up with extra copies of their entire set of DNA, a state called polyploidy. This happens often in plants and some animals, but in mammals its much less common and only seen in a few organs or during aging and disease, like cancer. To date it is not understand why some tissues can handle polyploid cells, while others cant, or what exactly these cells do in healthy organs. Previous researchmostly in lab-grown cells or non-mammalian speciesshows that polyploidy can change how cells behave. It can affect their size, how well they divide, and how they respond to DNA damage. But it is not known if these changes also happen in living mammals, or how polyploid cells influence the way tissues grow, function, or repair themselves. Interestingly, polyploid cells can appear during tissue healing. For example, in the kidney, they emerge after injury and may help trigger scarring (fibrosis). This suggests that polyploid cells might actively shape their surroundings, but their overall impact in living tissue is still unclear. The aim of this project is to understand where polyploid cells occur in the body, why certain cell types can tolerate having extra DNA, and how these cells affect their neighbors. To study this, Ill use a genetic mouse model that allows to create polyploid cells on demand. This will help me track how polyploid cells behave over time in different organs. In the second part of the project, Ill grow 3D mini-organs, termed organoids, from different tissues to investigate what makes some cells more adaptable to having extra DNA. Finally, Ill use advanced imaging and gene analysis tools to study how polyploid cells affect the cells around them in different tissues. While most research on polyploidy has focused on cancer or simple lab systems, this study will look at how polyploidy works in healthy mammalian tissues, across different ages and sexes. Since polyploid cells may contribute to scarring and tissue damagea big problem in many chronic diseasesunderstanding them better could help us find new ways to treat these conditions in the future.

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