Establishment of a patient-derived iPS cells for simulating myelodysplastic syndrome
Project/Area Number |
23591373
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Hematology
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Research Institution | The University of Tokyo |
Principal Investigator |
TOJO Arinobu 東京大学, 医科学研究所, 教授 (00211681)
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Co-Investigator(Renkei-kenkyūsha) |
KOBAYASHI Seiichiro 東京大学医科学研究所, 分子療法分野, 助教 (70376622)
IZAWA Kiyoko 東京大学医科学研究所, 分子療法分野, 特任研究員 (20534415)
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Project Period (FY) |
2011 – 2013
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Project Status |
Completed (Fiscal Year 2013)
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Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
|
Keywords | iPS細胞 / 骨髄異形成症候群(MDS) / 初期化因子 / レンチウイルスベクター / センダイウイルスベクター / CD34+細胞 / 骨髄異形成症候群 / CD34陽性細胞 / 細胞初期化 / 遺伝子変異 / MDS / レンチウイルス / Cre/loxP |
Research Abstract |
Lentiviral vectors expressing 4 reprogramming factors (Oct4, Sox3, Klf4 and c-Myc) driven by constitutive (EF1a) or inducible (Tet-on) promoter were newly prepared. We tried to reprogram CD34+ cells from 5 patients with MDS (RCMD 3, RARS 1, and MDS/MPD 1) as well as 1 patient with CML-CP by infection with either lentiviral vector. In each case, a number of cell mass resembling iPSC colony appeared over the MEF layer within 3 weeks of culture, but, unfortunately, none of these iPSC-like colonies developed stable cell lines. Then, we took alternative method using a Sendai virus that does not integrate into the host genome. As a result, a patient-derived iPSCs were successfully established from a male patient with RCMD at the very end of the research periods. Since the patient's bone marrow cells revealed normal karyotype, comparative genetic examination between the patient's granulocytes (MDS clone), T cells (normal clone) and iPSCs are required to identify the true origin of iPSCs.
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Report
(4 results)
Research Products
(76 results)
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[Journal Article] CADM1 expression and stepwise down-regulation of CD7 is closely associated with clonal selection of HTLV-1-infected T cells potentially evolving into adult T cell leukemia/lymphoma2014
Author(s)
Kobayashi S, Nakano K, Watanabe E, Ishigaki T, Ohno N, Yuji K, Oyaizu N, Asanuma S, Yamagishi M, Yamochi T, Watanabe N, Tojo A, Watanabe T, Uchimaru K
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Journal Title
Clin Cancer Res
Volume: 20(11)
Pages: 2851-2861
Related Report
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[Journal Article] miR-126-mediated control of cell fate in B cell-myeloid progenitors as a potential alternative to transcriptional factors2013
Author(s)
Okuyama K, Ikawa T, Harnprasopwat R, Lu J, Yamashita R, Ha D, Toyoshima T, Chanda B, Kawamata T, Yokoyama K, Gertner B, Wang S, Ando K, Lodish HF, Tojo A, Kawamoto H, Kotani A
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Journal Title
Proc Natl Acad Sci USA
Volume: 110(33)
Pages: 13410-5
Related Report
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[Journal Article] The CD3 versus CD7 plot in multicolor flow cytometry reflects progression of disease stage in patients infected with HTLV-I2013
Author(s)
Kobayashi S, Tian Y, Ohno N, Yuji K, Ishigaki T, Isobe M, Tsuda M, Oyaizu N, Watanabe E, Watanabe N, Tani K, Tojo A, Uchimaru K
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Journal Title
Related Report
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[Journal Article] Quantitative PCR detection of CEP110-FGFR1 fusion gene in a patient with 8p11 syndrome.2013
Author(s)
Yamamoto S, Ebihara Y, Mochizuki S, Kawakita T, Kato S, Ooi J, Takahashi S, Tojo A, Yusa N, Furukawa Y, Oyaizu N, Watanabe J, Sato K, Kimura F, Tsuji K.
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Journal Title
Leukemia and Lymphoma
Volume: 54
Issue: 9
Pages: 2068-2069
DOI
Related Report
Peer Reviewed
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[Journal Article] MicroRNA-126-mediated control of cell fate in B-cell myeloid progenitors as a potential alternative to transcriptional factors.2013
Author(s)
Okuyama K, Ikawa T, Gentner B, Hozumi K, Harnprasopwat R, Lu J, Yamashita R, Ha D, Toyoshima T, Chanda B, Kawamata T, Yokoyama K, Wang S, Ando K, Lodish HF, Tojo A, Kawamoto H, Kotani A
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Journal Title
Proc Natl Acad Sci U S A.
Volume: 110
Issue: 33
Pages: 13410-13415
DOI
Related Report
Peer Reviewed
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[Journal Article] The CD3 versus CD7 plot in multicolor flow cytometry reflects progression of disease stage in patients infected with HTLV-I.2013
Author(s)
Kobayashi S, Tian Y, Ohno N, Yuji K, Ishigaki T, Isobe M, Ohfuchi-Tsuda M, Oyaizu N, Watanabe E, Watanabe N, Tani K, Tojo A and Uchimaru K.
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Journal Title
PLoS One
Volume: 8
Issue: 1
Pages: e53728-e53728
DOI
Related Report
Peer Reviewed
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[Journal Article] Therapeutic outcome of multifocal Langerhans cell histiocytosis in adults treated with the Special C regimen formulated by the Japan LCH Study Group.2013
Author(s)
Morimoto A, Shimazaki C, Takahashi S, Yoshikawa K, Nishimura R, Wakita H, Kobayashi Y, Kanegane H, Tojo A, Imamura T, Imashuku S; Japan LCH Study Group.
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Journal Title
Int J Hematol.
Volume: 97
Issue: 1
Pages: 103-108
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] ErbB/NF-κB signaling controls mammosphere formation in human breast cancer2012
Author(s)
Hinohara K, Kobayashi S, Kanauchi H, Simizu S, Nishioka K, Tsuji E, Tada K, Umezawa K, Mori M, Ogawa T, Inoue J, Tojo A, Gotoh N
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Journal Title
Proc Natl Acad Sci USA
Volume: 109
Pages: 6584-9
Related Report
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[Journal Article] Imatinib mesylate directly impairs class switch recombination through downregulation of AID2012
Author(s)
Kawamata T, Jun L, Sato T, Tanaka M, Nagaoka H, Agata Y, Toyoshima T, Yokoyama K, Oyaizu N, Nakamura N, Ando K, Tojo A, Kotani A
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Journal Title
Blood
Volume: 119
Pages: 3123-7
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[Journal Article] Imatinib mesylate directly impairs class switch recombination through downregulation of AID.2012
Author(s)
Kawamata T, Lu J, Sato T, Tanaka M, Nagaoka H, Agata Y, Toyoshima T, Yokoyama K, Oyaizu N, Nakamura N, Ando K, Tojo A, Kotani A
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Journal Title
Blood
Volume: 119
Issue: 13
Pages: 3123-3127
DOI
Related Report
Peer Reviewed
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