HEMATOPOIETIC STEM-CELL MAINTENANCE AND DIFFERENTIATION ARE SUPPORTEDBY EMBRYONIC AORTA-GONAD-MESONEPHROS REGION-DERIVED ENDOTHELIUM

Hematopoietic stem cells are capable of extensive self-renewal and exp ansion, particularly during embryonic growth. Although the molecular m echanisms involved with stem cell maintenance remain mysterious, it is now clear that an intraembryonic location, the aorta-gonad-mesonephro s (AGM) region, is a site of residence and, potentially, amplification of the definitive hematopoietic stem cells that eventually seed the f etal liver and adult bone marrow. Because several studies suggested th at morphologically defined hematopoietic stem/progenitor cells in the AGM region appeared to be attached in clusters to the ventrally locate d endothelium of the dorsal aorta, we derived cell lines from this int raembryonic site using an anti-CD34 antibody to select endothelial cel ls. Analysis of two different AGM-derived CD34(+) cell lines revealed that one, DAS 104-8, efficiently induced fetal-liver hematopoietic ste m cells to differentiate down erythroid, myeloid, and B-lymphoid pathw ays, hut it did not mediate self-renewal of these pluripotent cells. I n 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 maintain ing fetal liver-derived hematopoietic stem cells able to competitively repopulate the bone marrow of lethally irradiated mice. These data bo lster the hypothesis that the endothelium of the AGM region acts to me diate the support and differentiation of hematopoietic stem cells in v ivo. (C) 1998 by The American Society of Hematology.