title: Efficient production of T cells from mouse pluripotent stem cells by controlled expression of Lhx2.
abstract: LIM-homeobox transcription factor Lhx2 induces ex vivo amplification of adult hematopoietic stem cells (HSCs) in mice. We previously showed that engraftable HSC-like cells are generated from mouse embryonic stem cells (ESCs) 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 ESCs carrying doxycycline (dox)-inducible Lhx2 expression cassette. Dox-mediated over-expression of Lhx2 conferred a self-renewing activity to ESC-derived c-Kit(+) CD41(+) embryonic hematopoietic progenitor cells (HPCs), 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, CD4/8 double negative T cells were detected in their thymi. Once the Lhx2 expression was terminated, differentiation of CD4/8 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 ESCs by the conditional expression of Lhx2.
authors.affiliation: Stem Cell Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kitajima
authors.affiliation: Stem Cell Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.|Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Manami
authors.initials: M
authors.lastname: Kawaguchi
authors.affiliation: Stem Cell Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.|Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Miyashita
authors.affiliation: Stem Cell Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.|Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Marino
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: Stem Cell Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.|Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Kanokoda
authors.affiliation: Stem Cell Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.|Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Hara
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004318:Doxycycline / Q000494:pharmacology; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000166:cytology; D060850:LIM-Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D060850:LIM-Homeodomain Proteins; C489784:Lhx2 protein, mouse; D014157:Transcription Factors; D004318:Doxycycline