Unravelling the pathways that mediate cell competition during embryonic differentiation

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At the beginning of development, the cells of the embryo start off with a very broad developmental potential, termed pluripotency. Pluripotent cells are not only important as they will give rise to all the cell types and tissues that will form the newborn organism, but also hold great promise for regenerative medicine due to their future clinical applications in cellular therapies and their use in the development of patient specific "disease-in-a-dish" approaches to understand human diseases. It is therefore key to understand the mechanisms that eliminate abnormal or defective pluripotent cells. We have identified one such mechanism, termed cell competition. We have shown that during cell competition, cells compare their relative fitness level, and those cells that are recognised as less fit than their neighbours are eliminated from the embryo. An important implication of cell competition is that the ability of a cell to expand is not only determinant on its own growth, but also on the behaviour of its neighbours. By eliminating suboptimal cells from the embryonic stem cells pool cell competition ensures the quality of the cells that will sustain the future development of the embryo, as well as form the germline (cells that will give rise to the next generation). Interestingly, we have also shown that cells with cancer mutations can behave like super-competitors and expand by eliminating normal cells. This suggests that in addition to the above quality control role, cell competition could be a new mechanism used by cancer cells expand in the tissue. Here we will unravel how cell competition is regulated. For this we will establish which are the pathways by which fit cells signal the elimination of less-fit cells. These experiments will give us insight not only into the ways in which the embryo deals with defective cells, but will also give us insight into other possible roles of cell competition in ensuring the fitness of ageing tissues and preventing the expansion of cancer cells.