Final Activity Report Summary - MYCHSC (Dissecting the role of Myc and Jun in hematopoietic stem cell self-renewal and cancer formation) In order to identify the role of the 'Tif1?' gene in blood (hematopoietic) development, we removed the activity of this gene in hematopoietic precursors in the early mouse embryo and analysed the subsequent blood phenotype. The first identifiable blood defect observed upon complete absence of Tif1? activity was a reduced number of hematopoietic stem cell (HSC) emergence from within the embryo. Prominent cell death of hematopoietic progenitors and erythroid (red blood cell) precursors was observed in the following 48hrs of development, ultimately leading to complete loss of foetal liver and placental HSC activity. Loss of Tif1? activity in blood precursor cells is incompatible with life and embryos die due to a lack of functional blood cells. Collectively, our data demonstrate that Tif1? is crucial for the generation, survival and functional activity of definitive HSCs.