Blood stem cells provide the constant supply of new blood cells throughout a person’s lifetime. Their transcriptional regulation, i.e. the fine tuning of which genes should be active at any given time, is critical for their normal function. Moreover, a large number of leukaemias arise, when this fine balance of gene activities is disturbed. However, very little is known about the molecular mechanisms responsible for setting the appropriate gene activities in blood stem cells. Transcription factors are responsible for controlling the activity of other genes and many of the transcription factors important for the normal function of blood stem cells are also active in the cell that forms blood platelets, the megakaryocyte. This proposal aims to compare the gene regulatory programs of blood stem cells and megakaryocytes. The focus will be on a triad of regulatory transcription factors: Gata2/Fli1/Scl, which have recently been shown to be essential for the development of blood cells during embryogenesis.
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