ROLE OF ENDOTHELIUM IN THE CONTROL OF MOUSE YOLK-SAC STEM-CELL DIFFERENTIATION

Studies in our laboratory have shown that as early as day 8.5 of devel opment, mouse yolk sac cells can generate T cells when placed in a thy mic microenvironment. At this stage, yolk sac cells can also different iate into myeloid cells in vitro. B cell differentiation in vitro was achieved with day 9 yolk sac by providing a bone marrow stromal feeder layer. We have now established endothelial cell Lines and clones from yolk sacs of day 8-12 mouse embryos, These vary in their ability to s upport stem cell maintenance and differentiation. Our principal work h as been carried out with day 12 cloned endothelial cell lines. One clo ne supported the >100 fold expansion of yolk sac hematopoietic stem ce lls that subsequently could generate B cells, T cells and myeloid cell s both in vitro and in vivo. Preliminary experiments with endothelial cells from younger embryos are also described. (C) 1998 Elsevier Scien ce Ltd. All rights reserved.