Efficient production of T cells from mouse pluripotent stem cells by controlled expression of Lhx2

LIM ‐homeobox transcription factor Lhx2 induces ex vivo amplification of adult hematopoietic stem cells ( HSC s) in mice. We previously showed that engraftable HSC ‐like cells are generated from mouse embryonic stem cells ( ESC s) and induced pluripotent stem cells by enforced expression of Lhx2 . However, when these HSC ‐like cells were transplanted into irradiated congenic mice, donor‐derived T cells were barely detectable, whereas other lineages of hematopoietic cells were continuously produced. Here we investigated T‐cell differentiation potential of the Lhx2 ‐induced HSC ‐like cells using ESC s carrying doxycycline (dox)‐inducible Lhx2 expression cassette. Dox‐mediated over‐expression of Lhx2 conferred a self‐renewing activity to ESC ‐derived c‐Kit + CD 41 + embryonic hematopoietic progenitor cells ( HPC s), thereby converting them to HSC ‐like cells. When these HSC ‐like cells were transplanted into irradiated immunodeficient mice and they were supplied with a dox‐containing water, CD 4/8 double negative T cells were detected in their thymi. Once the Lhx2 expression was terminated, differentiation of CD 4/8 double positive and single positive T cells was initiated in the thymi of transplanted mice and mature T cells were released in the peripheral blood. These results showed that engraftable HSC ‐like cells with full hematopoietic potential can be obtained from ESC s by the conditional expression of Lhx2 .