In vitro differentiation of embryonic stem cells into lymphocyte precursors able to generate T and B lymphocytes in vivo.

Embryonic stem cells can be induced in vitro, by coculture with the stromal line RP.0.10 and a mixture of interleukins 3, 6, and 7, to differentiate into T (Joro75+) and B (B-220+) lymphocyte progenitors and other (Thy-1+, PgP-1+, c-kit+, Joro75-, B-220-, F4/80-, Mac-1-) hemopoietic precursors. The progeny of in vitro-induced embryonic stem cells can reconstitute the lymphoid compartments of T- and B-lymphocyte-deficient scid mice and generate mature T and B lymphocytes in sublethally irradiated normal mice. Exogenous cytokines can dramatically alter the developmental fate of embryonic stem cells in culture. The in vitro system described here should facilitate the study of molecular events leading to cell-lineage commitment and to the formation of hemopoietic stem cells and their immediate lymphoid progeny.