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Blood, Vol. 92 No. 3 (August 1), 1998:
pp. 908-919
Hematopoietic Stem Cell Maintenance and Differentiation Are
Supported by Embryonic Aorta-Gonad-Mesonephros Region-Derived
Endothelium
Osamu Ohneda,
Christopher Fennie,
Zhong Zheng,
Christopher Donahue,
Hank La,
Ricardo Villacorta,
Belinda Cairns, and
Laurence A. Lasky
From the Departments of Molecular Oncology, Immunology, and
Pathology, Genentech, Inc, South San Francisco, CA.
Hematopoietic stem cells are capable of extensive self-renewal and
expansion, particularly during embryonic growth. Although the molecular
mechanisms involved with stem cell maintenance remain mysterious, it is
now clear that an intraembryonic location, the aorta-gonad-mesonephros
(AGM) region, is a site of residence and, potentially, amplification of
the definitive hematopoietic stem cells that eventually seed the fetal
liver and adult bone marrow. Because several studies suggested that
morphologically defined hematopoietic stem/progenitor cells in the AGM
region appeared to be attached in clusters to the ventrally located
endothelium of the dorsal aorta, we derived cell lines from this
intraembryonic site using an anti-CD34 antibody to select endothelial
cells. Analysis of two different AGM-derived CD34+ cell
lines revealed that one, DAS 104-8, efficiently induced fetal-liver
hematopoietic stem cells to differentiate down erythroid, myeloid, and
B-lymphoid pathways, but it did not mediate self-renewal of these
pluripotent cells. In contrast, a second cell line, DAS 104-4, was
relatively inefficient at the induction of hematopoietic differentiation. Instead, this line provoked the expansion of early
hematopoietic progenitor cells of the
lin CD34+Sca-1+c-Kit+
phenotype and was proficient at maintaining fetal liver-derived hematopoietic stem cells able to competitively repopulate the bone
marrow of lethally irradiated mice. These data bolster the hypothesis
that the endothelium of the AGM region acts to mediate the support and
differentiation of hematopoietic stem cells in vivo.
© 1998 by The American Society of Hematology.
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