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Hematopoietc Stem Cells emergence in the mouse embryo: function(s) of RUNX1 and its binding partner CBFbeta

Final Activity Report Summary - RUNX1 IN HSCS (Hematopoietc Stem Cells emergence in the mouse embryo: function(s) of RUNX1 and its binding partner CBFbeta)

During adult life, hematopoietic stem cells (HSCs) are responsible for the constant production of blood cells. The overall goal of this project is to further our understanding of molecular and cellular events controlling HSC generation and maintenance during embryogenesis.

During the achievement of part 1, we showed the precise expression pattern of RUNX1 and its patner CBFb, two key regulators of HSC development. Our results allow us to design a new strategy for functional studies of mouse HSC development.

HSC development is also tightly regulated by microenvironmental signals. During the achievement of part 2, we found that the BMP signalling pathway is involved in this regulation. Using a mouse model reporting BMP signalling activity, we correlated the localisation and the identity of BMP signalling and responsive cells during HSC developement. Our results provide new insights concerning the control of HSCs by BMPs and the functioning of the first microenvironment for HSCs.

During embryogenesis, HSCs are sequencially found in distinct sites. In human, cord blood is known to be an important source of HSCs used in blood-related therapies. During the achievement of part 3, we identify and characterised HSCs in the human placenta. Our studies provide important data to improve clinical use of HSCs.