{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:14:40Z","timestamp":1790421280981,"version":"4.1.0"},"reference-count":43,"publisher":"National Academy of Sciences","issue":"44","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,11,2]]},"abstract":"<jats:p>The conversion of mature somatic cells into pluripotent stem cells, both by nuclear transfer and transduction with specific \u201creprogramming\u201d genes, represents a major advance in regenerative medicine. Pluripotent stem cell lines can now be generated from an individual's own cells, facilitating the generation of immunologically acceptable stem cell-based therapeutics. Many cell types can undergo nuclear reprogramming, leading to the question of whether the identity of the reprogrammed cell of origin has a biological consequence. Peripheral blood, containing a mixture of T, B, NK, and myeloid cell types, represents one potential source of reprogrammable cells. In this study, we describe the unique case of mice derived from a reprogrammed T cell. These mice have prerearranged T-cell receptor (TCR) genes in all cells. Surprisingly, \u224850% of mice with prerearranged TCR genes develop spontaneous T cell lymphomas, which originate in the thymus. The lymphomas arise from developing T cells, and contain activated Notch1, similar to most human and mouse T-cell acute lymphoblastic lymphomas. Furthermore, lymphomagenesis requires the expression of both prerearranged TCR\u03b1 and TCR\u03b2 genes, indicating a critical role for TCR signaling. Furthermore, inhibitors of multiple branches of TCR signaling suppress lymphoma growth, implicating TCR signaling as an essential component in lymphoma proliferation. The lymphomagenesis in mice derived from a reprogrammed T cell demonstrates the deleterious consequences of misregulation of the TCR rearrangement and signaling pathways and illustrates one case of cellular reprogramming where the identity of the cell of origin has profound consequences.<\/jats:p>","DOI":"10.1073\/pnas.1013230107","type":"journal-article","created":{"date-parts":[[2010,10,19]],"date-time":"2010-10-19T00:19:23Z","timestamp":1287447563000},"page":"18939-18943","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":48,"title":["T-cell receptor-driven lymphomagenesis in mice derived from a reprogrammed T cell"],"prefix":"10.1073","volume":"107","author":[{"given":"Thomas","family":"Serwold","sequence":"first","affiliation":[{"name":"Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konrad","family":"Hochedlinger","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Center for Regenerative Medicine and Cancer Center, Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Swindle","sequence":"additional","affiliation":[{"name":"Complegen, Inc., Seattle, WA 98104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Hedgpeth","sequence":"additional","affiliation":[{"name":"Complegen, Inc., Seattle, WA 98104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Jaenisch","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research, Cambridge, MA 02142; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irving L.","family":"Weissman","sequence":"additional","affiliation":[{"name":"Stanford Institute of Stem Cell Biology and Regenerative Medicine, Stanford University Cancer Center, Stanford University, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,10,18]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.07.024"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature718"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2008.05.010"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08436"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1154884"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.2.928"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2304"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210766"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1102160"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.062050599"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830271142"},{"key":"e_1_3_3_12_2","first-page":"2089","article-title":"Oncogenic potential of a pre-T cell receptor lacking the TCR beta variable domain","volume":"12","author":"Jacobs H","year":"1996","unstructured":"H Jacobs, et al., Oncogenic potential of a pre-T cell receptor lacking the TCR beta variable domain. 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