2013 Fiscal Year Final Research Report
Evaluation of human iPSCs by neural differentaition and tumorigenicity
| Project/Area Number |
23689017
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Keio University |
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Principal Investigator |
OKADA Yohei 慶應義塾大学, 医学部, 訪問准教授 (30383714)
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| Project Period (FY) |
2011-11-18 – 2014-03-31
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| Keywords | ヒトiPS細胞 / 品質評価 / 神経分化 / 造腫瘍性 |
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| Research Abstract |
Human-induced pluripotent stem cells (hiPSCs) hold great promise for regenerative medicine. Despite the importance in evaluating their quality for future cell therapy, there are no precise analyses for assessing abnormal differentiation and tumorigenicity. We demonstrated that pre-evaluated hiPSC clones, established by retroviruses or integration-free episomal vectors, may exhibit glioma-like tumor formation by the transplantation of hiPSC-derived neural stem/progenitor cells into NOD/SCID mice. Notably, the tumorigenicities were closely associated with incomplete reprogramming of hiPSCs, revealed by the expressions of newly identified human embryonic stem cell signature genes or DNA repair genes. This incomplete reprogramming resulted in genomic instability not in an undifferentiated state, but during neural differentiation. Moreover, cluster of DNA repair genes may provide a useful "scorecard" for easy and quick evaluation of the incomplete reprogramming of hiPSCs.
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Research Products
(39 results)
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[Journal Article] Involvement of ER Stress in Dysmyelination of Pelizaeus-Merzbacher Disease with PLP1 Missense Mutations Shown by iPSC-Derived Oligodendrocytes2014
Author(s)
Numasawa-Kuroiwa Y, Okada Y#, Shibata S, Kishi N, Akamatsu W, Shoji M, Nakanishi A, Oyama M, Osaka H, Inoue K, Takahashi K, Yamanaka S, Kosaki K, Takahashi T, Okano H#(#corresponding authors)
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Journal Title
Stem Cell Report
Volume: 2(5)
Pages: 648-661
Peer Reviewed
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[Journal Article] Increased L1 Retrotransposition in the Neuronal Genome in Schizophrenia2014
Author(s)
Bundo M, Toyoshima M, Okada Y, Akamatsu W, Ueda J, Nemoto-Miyauchi T, Sunaga F, Toritsuka M, Ikawa D, Kakita A, Kato M, Kasai K, Kishimoto T, Nawa H, Okano H, Yoshikawa T, Kato T, Iwamoto K
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Journal Title
Neuron
Volume: 81(2)
Pages: 306-13
DOI
Peer Reviewed
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[Journal Article] A human Dravet syndrome model from patient induced pluripotent stem cells2013
Author(s)
Higurashi N, Uchida T, Christoph L, Misumi Y, Okada Y, Akamatsu W, Imaizumi Y, Zhang B, Nabeshima K, Mori MX, Katsurabayashi S, Shirasaka Y, Okano H, Hirose S
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Journal Title
Mol Brain
Volume: 6(1)
Pages: 19
DOI
Peer Reviewed
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[Journal Article] Decidua-Derived Mesenchymal Cells are a Promising Source for the Generation and Cell Banking, of Human Induced Pluripotent Stem Cells2013
Author(s)
Shofuda T, Kanematsu D, Fukusumi H, Yamamoto A, Bamba Y, Yoshitatsu S, Suemizu H, Nakamura M, Sugimoto Y, Furue KM, Kohara A, Akamatsu W, Okada Y, Okano H, Yamasaki M, Kanemura Y. Human
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Journal Title
Cell Medicine
Volume: 4(3)
Pages: 125-147
DOI
Peer Reviewed
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[Journal Article] Pre-Evaluated Safe Human iPSC-Derived Neural Stem Cells Promote Functional Recovery after Spinal Cord Injury in Common Marmoset without Tumorigenicity2012
Author(s)
Kobayashi Y, Okada Y, Itakura G, Iwai H, Nishimura S, Nori S, Hikishima K, Konomi T, Fujiyoshi K, Tsuji O, Toyama Y, Yamanaka S, Nakamura M, Okano H
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Journal Title
PLoS One
Volume: (12)
Pages: e52787
DOI
Peer Reviewed
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[Journal Article] Multiple analyses of G-protein coupled receptor (GPCR) expression in the development of gefitinib-resistance in transforming non-small-cell lung cancer2012
Author(s)
Kuzumaki N, Suzuki A, Narita M, Hosoya T, Nagasawa A, Imai S, Yamamizu K, Morita H, Suzuki T, Okada Y, Okano HJ, Yamashita JK, Okano H, Narita M.
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Journal Title
PLoS One
Volume: 7(10)
Pages: e44368
DOI
Peer Reviewed
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[Journal Article] Efficient Derivation of Multipotent Neural Stem/Progenitor Cells from Non-human Primate Embryonic Stem Cells2012
Author(s)
Shimada H, Okada Y, Ibata K, Ebise H, Ota S, Tomioka I, Nomura T, Maeda T, Kohda K, Yuzaki M, Sasaki E, Nakamura M, Okano H
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Journal Title
PLoS One
Volume: 7(11)
Pages: e49469
DOI
Peer Reviewed
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[Journal Article] Mitochondrial dysfunction associated with increased oxidativestress andα-synuclein accumulation in PARK2 iPSC-derived neurons and postmortem brain tissue2012
Author(s)
Imaizumi Y, Okada Y, Akamatsu W, Koike M, Kuzumaki N, Hayakawa H, Nihira T, Kobayashi T, Ohyama M, Sato S, Takanashi M, Funayama M, Hirayama A, Soga T, Hishiki T, Suematsu M, Yagi T, Ito D, Kosakai A, Hayashi K, Shouji M, Nakanishi A, Suzuki N, Mizuno Y, Mizushima N, Amagai M, Uchiyama Y, Mochizuki H, Hattori N, Okano H
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Journal Title
Mol. Brain
Volume: 5(1)
Pages: 35
DOI
Peer Reviewed
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[Journal Article] Establishment of induced pluripotent stem cells from centenarians for neurodegenerative disease research2012
Author(s)
Yagi T, Kosakai A, Ito D, Okada Y, Akamatsu W, Nihei Y, Nabetani A, Ishikawa F, Arai Y, Hirose N, Okano H, Suzuki N
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Journal Title
PLoS One
Volume: 7(7)
Pages: e41572
DOI
Peer Reviewed
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[Journal Article] RNA-Binding Protein Musashi1 Modulates Glioma Cell Growth through the Post-Transcriptional Regulation of Notch and PI(3) Kinase/Akt Signaling Pathways2012
Author(s)
Muto J, Imai T, Ogawa D, Nishimoto Y, Okada Y, Mabuchi Y, Kawase T, Iwanami A, Mischel PS, Saya H, Yoshida K, Matsuzaki Y, Okano H
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Journal Title
PLoS One
Volume: 7(3)
Pages: e33431
DOI
Peer Reviewed
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[Journal Article] Effect ofκ-opioid receptor agonist on the growth of non-small cell lung cancer (NSCLC) cells2011
Author(s)
Kuzumaki N, Suzuki A, Narita M, Hosoya T, Nagasawa A, Imai S, Yamamizu K, Morita H, Nagase H, Okada Y, Okano HJ, Yamashita JK, Okano H, Suzuki T, Narita M
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Journal Title
Br J Cancer
Volume: 106(6)
Pages: 1148-52
DOI
Peer Reviewed
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[Journal Article] Grafted human induced pluripotent stem cell-derived neurospheres promotes motor functional recovery after spinal cord injury in mice2011
Author(s)
Nori S, Okada Y, Yasuda A, Tsuji O, Takahashi Y, Kobayashi Y, Fujiyoshi K, Koike M, Uchiyama Y, Ikeda E, Toyama Y, Yamanaka S, Nakamura M, Okano H
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Journal Title
Proc Natl Acad Sci U S A
Volume: 108(40)
Pages: 16825-30
DOI
Peer Reviewed
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[Journal Article] Generation of human melanocytes from induced pluripotent stem cells2011
Author(s)
Ohta S, Imaizumi Y, Okada Y, Akamatsu W, Kuwahara R, Ohyama M, Amagai M, Matsuzaki Y, Yamanaka S, Okano H, Kawakami Y
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Journal Title
PlosOne
Volume: 6 (1)
Pages: e16182
DOI
Peer Reviewed
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[Journal Article] Gene targeting and subsequent site-specific transgenesis at theβ-actin (ACTB) locus in common marmoset embryonic stem cells2011
Author(s)
Shiozawa S, Kawai K, Okada Y, Tomioka I, Maeda T, Kanda A, Shinohara H, Suemizu H, Okano HJ, Sotomaru Y, Sasaki E, Okano H
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Journal Title
Stem Cells and Development
Volume: 20(9)(Epub 2011 Jan 16)
Pages: 1587-99
DOI
Peer Reviewed
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[Presentation] Incompletely reprogrammed human iPSCs form glioma-like tumors through genomic instability during neural differentiation2013
Author(s)
Okada Y, Miya, F, Koike M, Tomisato S, Tokura T, Ishihara Y, Shimojo D, Hattori C, Kanematsu D, Kanemura Y, Kohda K, Sobue G, Yamanaka S, Yuzaki M, Uchiyama Y, Ikeda E, Tsunoda T, Okano H
Organizer
The 11th Stem Cell Research Symposium
Place of Presentation
Tokyo Japan(シンポジウム)
Year and Date
2013-05-17
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