Molecular Identity of Hematopoietic Precursor Cells Emerging in the Human Embryo

It is now accepted from studies in animal models that hematopoieticstem cells emerge in the para-aortic mesoderm-derived aorta-gonad-mesonephros region of the vertebrate embryo. We have previously identified the equivalent primitive hematogenous territory in the 4- to 6-week human embryo, under the form ofCD34⁺CD45⁺Lin highproliferative potential hematopoietic cells clustered on the ventralendothelium of the aorta. To characterize molecules involved in initialstem cell emergence, we first investigated the expression in thatterritory of known early hematopoietic regulators. We herein show thataorta-associated CD34⁺ cells coexpress the tal-1/SCL,c-myb, GATA-2, GATA-3, c-kit, and flk-1/KDR genes, as do embryonic andfetal hematopoietic progenitors later present in the liver and bonemarrow. Next, CD34⁺CD45⁺ aorta-associatedcells were sorted by flow cytometry from a 5-week embryo and a cDNAlibrary was constructed therefrom. Differential screening of thatlibrary with total cDNA probes obtained from CD34⁺embryonic liver cells allowed the isolation of a kinase-related sequence previously identified in KG-1 cells. In addition to emerging blood stem cells, KG-1 kinase is also strikingly expressed in alldeveloping endothelial cells in the yolk sac and embryo, which suggestsits involvement in the genesis of both hematopoietic and vascular celllineages in humans.