In vitro differentiation of B cells and myeloid cells from the early mouse embryo and its extraembryonic yolk sac.

The yolk sac is the first site of hematopoiesis during ontogeny. However, the source of early embryonic hematopoietic stem cells remains unresolved. Early studies have shown that cells obtained from day-8 and -9 extraembryonic yolk sacs can give rise to T cells and myeloid cells, whereas the embryo itself appears to lack such cells. Controversy remains as to whether it is the embryo itself or the extraembryonic yolk sac that contains the initial precursors capable of differentiating into B cells. This study used the approach of enriching hematopoietic stem cells by immunocytoadherence and studying cells isolated from within the embryo itself or from the yolk sac obtained at days 8 and 9 of mouse embryonic development. We report that on day 9, both yolk sac-derived and embryo-derived cells can give rise to B cells and myeloid cells in vitro. On day 8, however, cells isolated from the yolk sac but not from the embryo produce myeloid colonies in vitro; neither source of stem cells generates B cells. Our study suggests that myeloid precursors migrate from yolk sac to embryo earlier than has previously been reported but that the origin for B cell precursors remains to be determined.