CD43, but not CD41 or GPI-80, marks first definitive haematopoietic stem cells in the human embryo

During mammalian embryonic development, haematopoietic stem cells (HSCs) first emerge in the aorta-gonad-mesonephros (AGM) region. Human definitive HSCs emerge in low numbers and reside within the VE-CAD+CD45+ population consisting of 500-1000 cells. Accurate identification of the first HSCs emerging within this population is important for understanding their biology and underlying developmental mechanisms. Here, we characterised the expression of potential markers labelling HSCs during their emergence in the AGM at Carnegie stages (CS) 14-17. We found that the first definitive HSCs are marked by CD43, but not CD41, similar to the early haematopoietic progenitor cells differentiating in culture from human embryonic stem cells. We show that, during development in the AGM region and in the beginning of liver colonisation, HSCs remain GPI-80 negative, in contrast to liver HSCs at the later midtrimester foetal development. Together with our previous observations, this study provides firm evidence that HSCs colonise human embryonic liver at CS17-18.