MOLECULAR IDENTITY OF HEMATOPOIETIC PRECURSOR CELLS EMERGING IN THE HUMAN EMBRYO

It is now accepted from studies in animal models that hematopoietic st em cells emerge in the para-aortic mesoderm-derived aorta-gonad-mesone phros region of the vertebrate embryo. We have previously identified t he equivalent primitive hematogenous territory in the 4- to 6-week hum an embryo, under the form of CD34(+)CD45(+)Lin(-) high proliferative p otential hematopoietic cells clustered on the ventral endothelium of t he aorta. To characterize molecules involved in initial stem cell emer gence, we first investigated the expression in that territory of known early hematopoietic regulators. We herein show that aorta-associated CD34(+) cells coexpress the tal-1/SCL, c-myb, GATA-2, GATA-8, c-kit, a nd flk-1/KDR genes, as do embryonic and fetal hematopoietic progenitor s later present in the liver and bone marrow. Next, CD34(+)CD45(+) aor ta-associated cells were sorted by flow cytometry from a B-week embryo and a cDNA library was constructed therefrom. Differential screening of that library with total cDNA probes obtained from CD34(+) embryonic liver cells allowed the isolation of a kinase-related sequence previo usly identified in KG-1 cells. In addition to emerging blood stem cell s, KG-1 kinase is also strikingly expressed in all developing endothel ial cells in the yolk sac and embryo, which suggests its involvement i n the genesis of both hematopoietic and vascular cell lineages in huma ns. (C) 1998 by The American Society of Hematology.