{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T12:49:38Z","timestamp":1772455778363,"version":"3.50.1"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,5,10]],"date-time":"2017-05-10T00:00:00Z","timestamp":1494374400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,5,10]],"date-time":"2017-05-10T00:00:00Z","timestamp":1494374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>B cell derived induced pluripotent stem cells (BiPSCs) were recently established from peripheral blood B cells by the simultaneous transfection of Yamanaka factors (Oct3\/4, Sox2, Klf4, c-Myc) and C\/EBP\u03b1 using a Sendai virus vector. Here, using a different method, we established BiPSCs with immunoglobulin heavy chain (IgH) gene rearrangement from normal B cells purified from lymph nodes. The critical points of our method are pre-stimulation of B cells with IL-21 and CD40-ligand (CD40L), followed by consecutive transfection of highly concentrated Yamanaka factors using a retroviral vector. Following each transfection the cells were centrifuged onto a retronectin coated plate and the activated by IL-4, IL-2, and CD40L. Furthermore, we established BiPSCs (BiPSC-A) in which activation-induced cytidine deaminase (AID) could be induced using the doxycycline-controlled. Both the parental BiPSC and BiPSC-A showed the capability of differentiating into hematopoietic progenitor cells (HPCs) based on confirmation of CD34 expression and colony-formation from CD34-positive cells. The findings that BiPSC-A can differentiate into HPCs suggest that there is a possibility that induction of AID expression would result in chromosomal translocations in the process of differentiation from BiPSCs, and therefore that these BiPSCs could be useful in elucidating the tumor origin of abnormal B cells in myelomagenesis.<\/jats:p>","DOI":"10.1038\/s41598-017-01627-1","type":"journal-article","created":{"date-parts":[[2017,5,4]],"date-time":"2017-05-04T10:10:52Z","timestamp":1493892652000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Establishment of induced pluripotent stem cells from normal B cells and inducing AID expression in their differentiation into hematopoietic progenitor cells"],"prefix":"10.1038","volume":"7","author":[{"given":"Fumihiko","family":"Kawamura","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Inaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Katafuchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Abe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4425-4526","authenticated-orcid":false,"given":"Naohiro","family":"Tsuyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumiko","family":"Kurosu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aki","family":"Yanagi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsunori","family":"Higuchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Muto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takumi","family":"Yamaura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideyoshi","family":"Noji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichi","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuaki A.","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megumi","family":"Sasatani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Kamiya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masafumi","family":"Onodera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Sakai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,5,10]]},"reference":[{"key":"1627_CR1","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","volume":"131","author":"K Takahashi","year":"2007","unstructured":"Takahashi, K. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. \n                           131, 861\u201372, doi:10.1016\/j.cell.2007.11.019 (2007).","journal-title":"Cell."},{"key":"1627_CR2","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1016\/j.cell.2008.07.041","volume":"134","author":"IH Park","year":"2008","unstructured":"Park, I. H. et al. Disease-specific induced pluripotent stem cells. Cell. \n                           134, 877\u201386, doi:10.1016\/j.cell.2008.07.041 (2008).","journal-title":"Cell."},{"key":"1627_CR3","doi-asserted-by":"publisher","first-page":"1920","DOI":"10.1126\/science.1152092","volume":"318","author":"J Hanna","year":"2007","unstructured":"Hanna, J. et al. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science. \n                           318, 1920\u201323, doi:10.1126\/science.1152092 (2007).","journal-title":"Science."},{"key":"1627_CR4","doi-asserted-by":"publisher","first-page":"9826","DOI":"10.1073\/pnas.0904689106","volume":"106","author":"L Ye","year":"2009","unstructured":"Ye, L. et al. Induced pluripotent stem cells offer new approach to therapy in thalassemia and sickle cell anemia and option in prenatal diagnosis in genetic diseases. Proc Natl Acad Sci USA \n                           106, 9826\u201330, doi:10.1073\/pnas.0904689106 (2009).","journal-title":"Proc Natl Acad Sci USA"},{"key":"1627_CR5","doi-asserted-by":"publisher","first-page":"2344","DOI":"10.1038\/leu.2014.136","volume":"28","author":"M Sakurai","year":"2014","unstructured":"Sakurai, M. et al. Impaired hematopoietic differentiation of RUNX1-mutated induced pluripotent stem cells derived from FPD\/AML patients. Leukemia. \n                           28, 2344\u201354, doi:10.1038\/leu.2014.136 (2014).","journal-title":"Leukemia."},{"key":"1627_CR6","doi-asserted-by":"publisher","first-page":"5473","DOI":"10.1182\/blood-2009-04-217406","volume":"114","author":"Z Ye","year":"2009","unstructured":"Ye, Z. et al. Human-induced pluripotent stem cells from blood cells of healthy donors and patients with acquired blood disorders. Blood. \n                           114, 5473\u201380, doi:10.1182\/blood-2009-04-217406 (2009).","journal-title":"Blood."},{"key":"1627_CR7","doi-asserted-by":"publisher","first-page":"4039","DOI":"10.1182\/blood-2009-07-231845","volume":"115","author":"JE Carette","year":"2010","unstructured":"Carette, J. E. et al. Generation of iPSCs from cultured human malignant cells. Blood. \n                           115, 4039\u201342, doi:10.1182\/blood-2009-07-231845 (2010).","journal-title":"Blood."},{"key":"1627_CR8","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1073\/pnas.0912407107","volume":"107","author":"N Miyoshi","year":"2010","unstructured":"Miyoshi, N. et al. Defined factors induce reprogramming of gastrointestinal cancer cells. Proc Natl Acad Sci USA. \n                           107, 40\u20135, doi:10.1073\/pnas.0912407107 (2010).","journal-title":"Proc Natl Acad Sci USA."},{"key":"1627_CR9","doi-asserted-by":"publisher","first-page":"6234","DOI":"10.1182\/blood-2011-07-367441","volume":"119","author":"K Kumano","year":"2012","unstructured":"Kumano, K. et al. Generation of induced pluripotent stem cells from primary chronic myelogenous leukemia patient samples. Blood. \n                           119, 6234\u201342, doi:10.1182\/blood-2011-07-367441 (2012).","journal-title":"Blood."},{"key":"1627_CR10","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.stem.2012.11.002","volume":"12","author":"T Nishimura","year":"2013","unstructured":"Nishimura, T. et al. Generation of rejuvenated antigen-specific T cells by reprogramming to pluripotency and redifferentiation. Cell Stem Cell \n                           12, 114\u201326, doi:10.1016\/j.stem.2012.11.002 (2013).","journal-title":"Cell Stem Cell"},{"key":"1627_CR11","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.stem.2012.12.006","volume":"12","author":"R Vizcardo","year":"2013","unstructured":"Vizcardo, R. et al. Regeneration of human tumor antigen-specific T cells from iPSCs derived from mature CD8(+) T cells. Cell Stem Cell. \n                           12, 31\u20136, doi:10.1016\/j.stem.2012.12.006 (2013).","journal-title":"Cell Stem Cell."},{"key":"1627_CR12","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/j.cell.2008.03.028","volume":"133","author":"J Hanna","year":"2008","unstructured":"Hanna, J. et al. Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell. \n                           133, 250\u201364, doi:10.1016\/j.cell.2008.03.028 (2008).","journal-title":"Cell."},{"key":"1627_CR13","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1093\/intimm\/dxq458","volume":"23","author":"H Wada","year":"2011","unstructured":"Wada, H. et al. Successful differentiation to T cells, but unsuccessful B-cell generation, from B-cell-derived induced pluripotent stem cells. 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Leukemia. \n                           30, 674\u201382, doi:10.1038\/leu.2015.294 (2016).","journal-title":"Leukemia."},{"key":"1627_CR16","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/S0092-8674(00)00078-7","volume":"102","author":"M Muramatsu","year":"2000","unstructured":"Muramatsu, M. et al. Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell. \n                           102, 553\u201363, doi:10.1016\/S0092-8674(00)00078-7 (2000).","journal-title":"Cell."},{"key":"1627_CR17","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1038\/35085588","volume":"412","author":"L Pasqualucci","year":"2001","unstructured":"Pasqualucci, L. et al. Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas. 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PLoS One. \n                           7, e40332, doi:10.1371\/journal.pone.0040332 (2012).","journal-title":"PLoS One."},{"key":"1627_CR22","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1038\/nrc.2016.40","volume":"16","author":"MR Lieber","year":"2016","unstructured":"Lieber, M. R. Mechanisms of human lymphoid chromosomal translocations. Nat Rev Cancer. \n                           16, 387\u201398, doi:10.1038\/nrc.2016.40 (2016).","journal-title":"Nat Rev Cancer."},{"key":"1627_CR23","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1182\/blood-2015-02-628164","volume":"127","author":"X Gu","year":"2012","unstructured":"Gu, X., Booth, C. J., Liu, Z. & Strout, M. P. AID-associated DNA repair pathways regulate malignant transformation in a murine model of BCL6-driven diffuse large B-cell lymphoma. 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Leukemia. \n                           17, 2257\u2013317, doi:10.1038\/sj.leu.2403202 (2003).","journal-title":"Leukemia."},{"key":"1627_CR32","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1111\/j.1349-7006.2011.02186.x","volume":"103","author":"H Shikata","year":"2012","unstructured":"Shikata, H. et al. Role of activation-induced cytidine deaminase in the progression of follicular lymphoma. Cancer Sci. \n                           103, 415\u201321, doi:10.1111\/j.1349-7006.2011.02186.x (2012).","journal-title":"Cancer Sci."},{"key":"1627_CR33","doi-asserted-by":"publisher","first-page":"5298","DOI":"10.1182\/blood-2007-10-117622","volume":"111","author":"N Takayama","year":"2008","unstructured":"Takayama, N. et al. Generation of functional platelets from human embryonic stem cells in vitro via ES-sacs, VEGF-promoted structures that concentrate hematopoietic progenitors. Blood. \n                           111, 5298\u2013306, doi:10.1182\/blood-2007-10-117622 (2008).","journal-title":"Blood."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-01627-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-01627-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-01627-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T04:10:41Z","timestamp":1671768641000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-01627-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,10]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["1627"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-01627-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,10]]},"assertion":[{"value":"24 October 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 May 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"1659"}}