title: Lineage marker-negative lymphocyte precursors derived from embryonic stem cells in vitro differentiate into mature lymphocytes in vivo.
abstract: We induced differentiation of mouse embryonic stem (ES) cells into lymphoid cells by culturing in methylcellulose, followed by the co-culture with a bone marrow stromal cell line ST2 in the presence of IL-7. These lymphoid cells expressed transcripts of the recombination activating genes, RAG-1 and RAG-2, as well as the C mu gene, although the lymphoid cells did not express surface antigens specific to T or B lymphocytes such as T200, CD4, CD8 and B220, or transcripts of B lymphocyte-specific genes such as lambda 5 and mb-1. D-J rearrangement was detectable in the lymphoid cells differentiated from ES cells in vitro and a sizeable number of both B and T lymphocytes were generated in vivo when the ES-derived lymphoid cells were transferred into RAG-2-deficient mice, which contain no B or T lymphocytes. The results indicate that in the in vitro co-culture system, ES cells give rise to immature lymphocyte precursors which have potentials to differentiate into both mature B and T lymphocytes in vivo. The ES-derived lineage marker-negative lymphocyte precursors would thus provide useful materials for studying early events of lymphopoiesis.
authors.affiliation: Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nisitani
authors.forename: T
authors.initials: T
authors.lastname: Tsubata
authors.forename: T
authors.initials: T
authors.lastname: Honjo
mesh_terms: D000818:Animals; D001483:Base Sequence; D001755:Blastocyst / Q000166:cytology; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D004268:DNA-Binding Proteins; D005434:Flow Cytometry; D015321:Gene Rearrangement; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D016131:Lymphocyte Subsets / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics; D017154:Stromal Cells / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D011506:Proteins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2