We have previously demonstrated the immune reconstitution benefits of co-administration of in vitro-derived lymphoid precursors in hematopoietic stem cell (HSC) and bone marrow (BM) transplantation settings. We are now exploring the mechanisms through which these precursors, generated in a Notch-based culture system, mediate their effects post-transplant. Our studies focus on improved HSC and BM engraftment, as well as fully characterizing effects on the thymus including thymic homing. In addition, we are investigating the lineage potential of in vitro-derived precursors both in vitro and in lethally irradiated recipients.