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Blood, Vol. 92 No. 10 (November 15), 1998:
pp. 3624-3635
Molecular Identity of Hematopoietic Precursor Cells
Emerging in the Human Embryo
Marie-Claude Labastie,
Fernando Cortés,
Paul-Henri Roméo,
Catherine Dulac, and
Bruno Péault
From Institut d'Embryologie Cellulaire et Moléculaire-CNRS UPR
9064, Nogent-sur-Marne, France; Unité de Recherche en
Hématopoïèse Moléculaire-INSERM U474,
Hôpital Henri Mondor, Créteil, France; and the Department
of Molecular and Cellular Biology, Howard Hughes Medical Institute,
Harvard University, Cambridge, MA.
It is now accepted from studies in animal models that hematopoietic
stem 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 of
CD34+CD45+Lin high
proliferative potential hematopoietic cells clustered on the ventral
endothelium of the aorta. To characterize molecules involved in initial
stem cell emergence, 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-3, c-kit, and flk-1/KDR genes, as do embryonic and
fetal hematopoietic progenitors later present in the liver and bone
marrow. Next, CD34+CD45+ aorta-associated
cells were sorted by flow cytometry from a 5-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 previously identified in KG-1 cells. In addition to emerging blood stem cells, KG-1 kinase is also strikingly expressed in all
developing endothelial cells in the yolk sac and embryo, which suggests
its involvement in the genesis of both hematopoietic and vascular cell
lineages in humans.
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