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Programming blood stem cells during embryonic development
Cells are programmed during embryonic development. As they move through the embryo, they receive signals from neighbouring cells thereby establishing their gene expression programmes. The agents of this programming are transcription factors whose expression is initially controlled by the embryonic signals and therefore by other transcription factors. Transcriptional regulatory networks are established, which become independent of the initiating signals but may remain dependent on maintenance signalling. Thus, as cells differentiate and arrive in their niches, their networks become stabilised. Understanding how these networks are established and maintained is the main interest of our lab. Our focus was on blood and the cardiovascular system. We had a particular interest in the programming of blood stem cells, an understanding of which will inform our understanding of many diseases including leukaemias. For example, genetic and environmental insults can be modelled and both the consequences and actions that might induce recovery can be predicted. In addition, realising the potential of stem cells to repair damaged or lost tissue will depend on the ability to manipulate these cells which in turn will benefit from a better understanding of these molecular circuitries.
We studied these processes in amphibia and fish (Xenopus and zebrafish) using techniques that manipulated signalling regimes and transcription factor activities in embryos as they develop. In addition, we studied development in embryo explants to simplify development in defined conditions, to define how embryos programme blood and the cardiovascular system.