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Niche signals and competitiveness
We have identified 3 major conserved signalling pathways that control the competitive ability of cyst stem cells (CySCs) in the testis, these are Hedgehog (Hh), Hippo (Hpo) and Ras/MAPK. Importantly, Ras/MAPK acts in a very similar manner in Drosophila CySCs and in mouse intestinal stem cells, suggesting our work will help understand fundamental stem cell behaviours. Ras gain of function leads to intestinal tumours, and the first step involves the mutant stem cell out-competing neighbouring wild type cells.
We use live imaging to follow stem cell replacement dynamics and study how these signals affect stem cell behaviour. We are also using large-scale sequencing approaches to find transcriptional targets of each signal, and find genes that could identify competitive stem cells.