Haematopoietic stem cells (HSCs) develop in the aorta-gonad-mesonephros (AGM) region. In utero development significantly reduces accessibility of the mouse embryo for analysis. We established AGM in vitro systems that can recapitulate in vivo HSC development, which allowed us to reconstruct and functionally validate the hierarchical organisation of HSC development. The first HSCs emerge in small numbers, possess an enormous regenerative/ self-renewing potential and can generate hundreds of fully functional daughter HSCs. We revealed a highly heterogeneous signalling landscape that can regulate HSC development in a concerted manner. In this talk, commonalities and differences in mouse and human development will be discussed.