The emergence of haematopoietic stem cells (HSCs) during early mammalian development is crucial for the formation of all blood cell lineages. Previous studies indicate that Runx1 is required for the endothelial-haematopoietic transition that gives rise to definitive HSCs; however, this transition occurs in multiple steps and the precise stage at which Runx1 is required has been unclear. In this issue (p. ), Alexander Medvinsky and colleagues define the exact point during murine HSC emergence at which Runx1 is required. Using a conditional reversible knockout strategy, the authors show that a deficiency of Runx1 does not affect commitment to the haematopoietic lineage as marked by the expression of CD41, as Runx1 knockout embryos still contain a population of CD41+ cells that can form HSCs when Runx1 expression is restored. However, the absence of Runx1 blocks progression to the next stage of HSC emergence, as marked by the expression of CD45. These results demonstrate a precise, stage-specific role for Runx1 in the molecular regulation of HSC emergence during embryo development.
