HP/HSC hierarchy defined by VE-cadherin in the human EL. (A) During human embryonic development, different waves of VE-cadherin⁺CD34⁺CD45⁻ hemogenic ECs are produced in the YS, AGM, and potentially in the placenta (Pl). These hemogenic ECs give rise to VE-cadherin⁺CD34⁺CD45⁺ 34DP cells that migrate to the EL. Very quickly after EL colonization, VE-cadherin is lost in the progeny of 34DP cells. This progeny (34HCP) is composed of VE-cadherin⁻CD34⁺CD45⁺ cells that display in vitro high proliferation, self-renewal and extended LTC-IC capacity, as well as LT-SRC ability in vivo, and could represent 34pre-HC cells. Eventually, 34HCP cells will end up giving rise to the classical VE-cadherin⁻CD34⁺CD45⁺ 34HCs, endowed with in vitro low proliferating, self-renewal, and standard LTC-IC capacity, as well as ST-SRC ability in vivo. (B) Schematic representation of the transitions of the various HCs populations in the human EL during development. LT-SRC, long-term SCID repopulating cells; ST-SRC, short-term SCID repopulating cells.