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Systematic Cellular Disease Models Reveal Synergistic Interaction of Trisomy 21 and GATA1 Mutations in Hematopoietic Abnormalities
http://hdl.handle.net/2241/00143099
http://hdl.handle.net/2241/00143099d89d284b-98a0-4fb3-ac63-129982055dc0
名前 / ファイル | ライセンス | アクション |
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CR_15-6 (2.3 MB)
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Item type | Journal Article(1) | |||||
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公開日 | 2016-07-06 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Systematic Cellular Disease Models Reveal Synergistic Interaction of Trisomy 21 and GATA1 Mutations in Hematopoietic Abnormalities | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_6501 | |||||
タイプ | journal article | |||||
アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
著者 |
Banno, Kimihiko
× Banno, Kimihiko× Omori, Sayaka× Hirata, Katsuya× Nawa, Nobutoshi× Nakagawa, Natsuki× 西村, 健× Ohtaka, Manami× Nakanishi, Mahito× Sakuma, Tetsushi× Yamamoto, Takashi× Toki, Tsutomu× Ito, Etsuro× Yamamoto, Toshiyuki× Kokubu, Chikara× Takeda, Junji× Taniguchi, Hidetoshi× Arahori, Hitomi× Wada, Kazuko× Kitabatake, Yasuji× Ozono, Keiichi |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Chromosomal aneuploidy and specific gene mutations are recognized early hallmarks of many oncogenic processes. However, the net effect of these abnormalities has generally not been explored. We focused on transient myeloproliferative disorder (TMD) in Down syndrome, which is characteristically associated with somatic mutations in GATA1. To better understand functional interplay between trisomy 21 and GATA1 mutations in hematopoiesis, we constructed cellular disease models using human induced pluripotent stem cells (iPSCs) and genome-editing technologies. Comparative analysis of these engineered iPSCs demonstrated that trisomy 21 perturbed hematopoietic development through the enhanced production of early hematopoietic progenitors and the upregulation of mutated GATA1, resulting in the accelerated production of aberrantly differentiated cells. These effects were mediated by dosage alterations of RUNX1, ETS2, and ERG, which are located in a critical 4-Mb region of chromosome 21. Our study provides insight into the genetic synergy that contributes to multi-step leukemogenesis. | |||||
言語 | en | |||||
書誌情報 |
en : Cell Reports 巻 15, 号 6, p. 1228-1241, 発行日 2016-05 |
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ISSN | ||||||
収録物識別子タイプ | PISSN | |||||
収録物識別子 | 2211-1247 | |||||
PubMed番号 | ||||||
識別子タイプ | PMID | |||||
関連識別子 | 27134169 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1016/j.celrep.2016.04.031 | |||||
権利 | ||||||
言語 | en | |||||
権利情報 | (c) 2016 The Authors. | |||||
権利 | ||||||
言語 | en | |||||
権利情報 | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). | |||||
出版タイプ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
出版者 | ||||||
言語 | en | |||||
出版者 | Cell Press |