DEVELOPMENT OF MOUSE EMBRYONIC STEM (ES) CELLS - IV DIFFERENTIATION TO MATURE T-LYMPHOCYTES AND B-LYMPHOCYTES AFTER IMPLANTATION OF EMBRYOID BODIES INTO NUDE-MICE

Mouse embryonic stem (ES) cells in culture can differentiate into late stages of many lineage-committed precursor cells. Under appropriate o rgan-culture conditions, ES cells differentiate into lymphoidlike cell s at a stage equivalent to lymphoid cells found in fetal liver. These hematopoietic precursors are located in cup-shaped structures found in some embryoid bodies; we called such embryoid bodies ''ES fetuses.'' In this study, we have followed the maturation of hematopoietic cells after implantation of ES fetuses into nude mice for 3 weeks. ES-cell-d erived lymphoid cells-pre-B cells, mature B cells, and mature T cells were found in all lymphoid organs. Interestingly, there was also an in crease of T cells of host origin. Because native nude mouse lack thymu s, these T cells might be educated by thymuslike epithelium generated from ES fetuses. Practical applications of this combined in vitro and in vivo system are discussed.