Reconstitution of Hematopoiesis Following Transplantation Into Neonatal Mice

The primary sites of hematopoiesis change during murine ontogeny. The first blood cells emerge in two waves in the yolk sac; primitive erythroblasts, megakaryocytes, and macrophages emerge on embryonic d (E) 7.0, whereas definitive progenitor cells appear as clusters within the yolk sac vasculature on E8.25. Of interest, yolk sac cells isolated prior to d 10.5 fail to engraft in myeloablated adult recipient mice and do not reconstitute hematopoiesis. We describe a method of sublethally myeloablating newborn mice in which E9.0 yolk sac cells engraft and repopulate all lineages of the hematopoietic system for up to 12 mo in primary recipients and up to 6 mo in secondary recipients. The exact mechanisms that permit yolk sac engraftment in the conditioned newborn mice remain elusive, but this method has been used by a number of investigators to pursue transplantation studies using embryo- or fetal-derived donor cells.