{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T08:16:06Z","timestamp":1740125766524,"version":"3.37.3"},"reference-count":42,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2015,7,7]],"date-time":"2015-07-07T00:00:00Z","timestamp":1436227200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24591415"],"award-info":[{"award-number":["24591415"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"a Health Labour Sciences Research Grant from the Ministry of Health Labour and Welfare"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:p><jats:styled-content style=\"fixed-case\">LIM<\/jats:styled-content>\u2010homeobox transcription factor <jats:italic>Lhx2<\/jats:italic> induces <jats:italic>ex\u00a0vivo<\/jats:italic> amplification of adult hematopoietic stem cells (<jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s) in mice. We previously showed that engraftable <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\u2010like cells are generated from mouse embryonic stem cells (<jats:styled-content style=\"fixed-case\">ESC<\/jats:styled-content>s) and induced pluripotent stem cells by enforced expression of <jats:italic>Lhx2<\/jats:italic>. However, when these <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\u2010like cells were transplanted into irradiated congenic mice, donor\u2010derived T cells were barely detectable, whereas other lineages of hematopoietic cells were continuously produced. Here we investigated T\u2010cell differentiation potential of the <jats:italic>Lhx2<\/jats:italic>\u2010induced <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\u2010like cells using <jats:styled-content style=\"fixed-case\">ESC<\/jats:styled-content>s carrying doxycycline (dox)\u2010inducible <jats:italic>Lhx2<\/jats:italic> expression cassette. Dox\u2010mediated over\u2010expression of <jats:italic>Lhx2<\/jats:italic> conferred a self\u2010renewing activity to <jats:styled-content style=\"fixed-case\">ESC<\/jats:styled-content>\u2010derived c\u2010Kit<jats:sup>+<\/jats:sup><jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>41<jats:sup>+<\/jats:sup> embryonic hematopoietic progenitor cells (<jats:styled-content style=\"fixed-case\">HPC<\/jats:styled-content>s), thereby converting them to <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\u2010like cells. When these <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\u2010like cells were transplanted into irradiated immunodeficient mice and they were supplied with a dox\u2010containing water, <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4\/8 double negative T cells were detected in their thymi. Once the <jats:italic>Lhx2<\/jats:italic> expression was terminated, differentiation of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>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 <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\u2010like cells with full hematopoietic potential can be obtained from <jats:styled-content style=\"fixed-case\">ESC<\/jats:styled-content>s by the conditional expression of <jats:italic>Lhx2<\/jats:italic>.<\/jats:p>","DOI":"10.1111\/gtc.12266","type":"journal-article","created":{"date-parts":[[2015,7,7]],"date-time":"2015-07-07T12:12:07Z","timestamp":1436271127000},"page":"720-738","source":"Crossref","is-referenced-by-count":7,"title":["Efficient production of T cells from mouse pluripotent stem cells by controlled expression of <i>Lhx2<\/i>"],"prefix":"10.1111","volume":"20","author":[{"given":"Kenji","family":"Kitajima","sequence":"first","affiliation":[{"name":"Stem Cell Project Tokyo Metropolitan Institute of Medical Science 2\u20101\u20106 Kamikitazawa Setagaya\u2010ku Tokyo 156\u20108506 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manami","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"Stem Cell Project Tokyo Metropolitan Institute of Medical Science 2\u20101\u20106 Kamikitazawa Setagaya\u2010ku Tokyo 156\u20108506 Japan"},{"name":"Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University 1\u20105\u201045 Yushima, Bunkyo\u2010ku Tokyo 113\u20108510 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuya","family":"Miyashita","sequence":"additional","affiliation":[{"name":"Stem Cell Project Tokyo Metropolitan Institute of Medical Science 2\u20101\u20106 Kamikitazawa Setagaya\u2010ku Tokyo 156\u20108506 Japan"},{"name":"Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University 1\u20105\u201045 Yushima, Bunkyo\u2010ku Tokyo 113\u20108510 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marino","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Stem Cell Project Tokyo Metropolitan Institute of Medical Science 2\u20101\u20106 Kamikitazawa Setagaya\u2010ku Tokyo 156\u20108506 Japan"},{"name":"Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University 1\u20105\u201045 Yushima, Bunkyo\u2010ku Tokyo 113\u20108510 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mai","family":"Kanokoda","sequence":"additional","affiliation":[{"name":"Stem Cell Project Tokyo Metropolitan Institute of Medical Science 2\u20101\u20106 Kamikitazawa Setagaya\u2010ku Tokyo 156\u20108506 Japan"},{"name":"Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University 1\u20105\u201045 Yushima, Bunkyo\u2010ku Tokyo 113\u20108510 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiko","family":"Hara","sequence":"additional","affiliation":[{"name":"Stem Cell Project Tokyo Metropolitan Institute of Medical Science 2\u20101\u20106 Kamikitazawa Setagaya\u2010ku Tokyo 156\u20108506 Japan"},{"name":"Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University 1\u20105\u201045 Yushima, Bunkyo\u2010ku Tokyo 113\u20108510 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,7,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00697-9"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.7.2720"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/11970"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08764"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2011.10.003"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2012.12.009"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.02.009"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1524207"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-169X.2007.00925.x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/77819"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300251"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt567"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.042119"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1500"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-07-298596"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(03)65005-6"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-472X(03)00261-3"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00680-3"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07679"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1392.006"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1188989"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004820"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.24.9003-9013.2003"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1182378"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80165-8"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012413"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-12-323212"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/416099a"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1316"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0505624102"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.19.5744"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.11.3939"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.15.2935"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-329516"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2010.00964.x"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1055"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00474-0"},{"key":"e_1_2_6_39_1","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1182\/blood.V94.8.2605.420k19_2605_2612","article-title":"Enhanced 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