Updated on 2024/10/02

Information

 

写真a

 
OHISHI HIROAKI
 
Organization
Medical Institute of Bioregulation Medical Research Center for High Depth Omics Assistant Professor
Graduate School of Systems Life Sciences Department of Systems Life Sciences(Joint Appointment)
Title
Assistant Professor
Contact information
メールアドレス
Tel
0926426882
Profile
The use of fluorescence imaging in multispatial omics technologies represents a groundbreaking approach that allows for the observation of the localization of DNA, RNA, and proteins at the single-cell level. Efforts are being made to enhance the detection sensitivity of molecular species, aiming for the development of more precise technologies. This advancement facilitates the analysis of intricate and large-scale intranuclear biological phenomena. Furthermore, by integrating high-precision visualization techniques for the simultaneous imaging of specific gene transcription and gene loci, progress is being made in elucidating the mechanisms of transcriptional regulation by higher-order genome structures.

Research Interests・Research Keywords

  • Research theme:The goal is to elucidate the gene transcription regulation mechanisms mediated by genome imprinting. Genome imprinting is a phenomenon where differences in gene expression levels between alleles arise due to differences in the epigenomes of males and females, particularly in DNA methylation. This regulatory mechanism is modulated by multiple factors, including the higher-order genome structure within the nucleus, transcriptional repressors, and transcription co-factors. To uncover the details of this molecular mechanism, research is being conducted using specific areas of live-cell imaging and multispatial omics technologies. Since disruptions in genome imprinting can lead to hereditary diseases, understanding its intricate control mechanisms lays the foundation for elucidating the pathophysiology of human diseases and developing therapeutic strategies.

    Keyword:Genomic imprinting

    Research period: 2023.3

Awards

  • 若手優秀発表賞

    2023.6   日本細胞生物学会  

  • ポスター優秀研究員賞

    2022.6   日本ゲノム編集学会  

  • 最優秀ポスター賞

    2014.7   第17回生医研リトリート2014  

Papers

  • Image Analysis Protocol for DNA/RNA/Immunofluorescence (IF)-seqFISH Data. International journal

    Hiroaki Ohishi, Hiroshi Ochiai

    Methods in molecular biology (Clifton, N.J.)   2856   419 - 432   2025   ISSN:1064-3745

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    Imaging-based spatial multi-omics technologies facilitate the analysis of higher-order genomic structures, gene transcription, and the localization of proteins and posttranslational modifications (PTMs) at the single-allele level, thereby enabling detailed observations of biological phenomena, including transcription machinery within cells and tissues. This chapter details the principles of such technologies, with a focus on DNA/RNA/immunofluorescence (IF) sequential fluorescence in situ hybridization (seqFISH). A comprehensive step-by-step protocol for image analysis is provided, covering image preprocessing, spot detection, and data visualization. For practical application, complete Jupyter Notebook codes are made available on GitHub ( https://github.com/Ochiai-Lab/seqFISH_analysis ).

    DOI: 10.1007/978-1-0716-4136-1_24

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  • Anti-phase clustering of regulatory factors shapes gene bursting

    Bitong Li, Yew Yan Wong, Neftali Flores-Rodriguez, Tara Davidson, Matthew S Graus, Valeriia Smialkovska, Hiroaki Ohishi, Angelika Feldmann, Hiroshi Ochiai, Mathias Francois

    bioRxiv   2024.9

  • Precise immunofluorescence canceling for highly multiplexed imaging to capture specific cell states Reviewed

    Kosuke Tomimatsu, Takeru Fujii, Ryoma Bise, Kazufumi Hosoda, Yosuke Taniguchi, Hiroshi Ochiai, Hiroaki Ohishi, Kanta Ando, Ryoma Minami, Kaori Tanaka, Taro Tachibana, Seiichi Mori, Akihito Harada, Kazumitsu Maehara, Masao Nagasaki, Seiichi Uchida, Hiroshi Kimura, Masashi Narita, Yasuyuki Ohkawa

    Nature Communications   15 ( 1 )   3657   2024.5   eISSN:2041-1723

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41467-024-47989-9

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  • Combined and differential roles of ADD domains of DNMT3A and DNMT3L on DNA methylation landscapes in mouse germ cells Reviewed

    Naoki Kubo, Ryuji Uehara, Shuhei Uemura, Hiroaki Ohishi, Kenjiro Shirane, Hiroyuki Sasaki

    Nature Communications   15 ( 1 )   3266   2024.4   eISSN:2041-1723

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    Abstract

    DNA methyltransferase 3A (DNMT3A) and its catalytically inactive cofactor DNA methyltransferase 3-Like (DNMT3L) proteins form functional heterotetramers to deposit DNA methylation in mammalian germ cells. While both proteins have an ATRX-DNMT3-DNMT3L (ADD) domain that recognizes histone H3 tail unmethylated at lysine-4 (H3K4me0), the combined and differential roles of the domains in the two proteins have not been fully defined in vivo. Here we investigate DNA methylation landscapes in female and male germ cells derived from mice with loss-of-function amino acid substitutions in the ADD domains of DNMT3A and/or DNMT3L. Mutations in either the DNMT3A-ADD or the DNMT3L-ADD domain moderately decrease global CG methylation levels, but to different degrees, in both germ cells. Furthermore, when the ADD domains of both DNMT3A and DNMT3L lose their functions, the CG methylation levels are much more reduced, especially in oocytes, comparable to the impact of the Dnmt3a/3L knockout. In contrast, aberrant accumulation of non-CG methylation occurs at thousands of genomic regions in the double mutant oocytes and spermatozoa. These results highlight the critical role of the ADD-H3K4me0 binding in proper CG and non-CG methylation in germ cells and the various impacts of the ADD domains of the two proteins.

    DOI: 10.1038/s41467-024-47699-2

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    Other Link: https://www.nature.com/articles/s41467-024-47699-2

  • Transcription-coupled changes in higher-order genomic structure and transcription hub viscosity prolong enhancer-promoter connectivity

    Hiroaki Ohishi, Soya Shinkai, Hitoshi Owada, Takeru Fujii, Kazufumi Hosoda, Shuichi Onami, Takashi Yamamoto, Yasuyuki Ohkawa, Hiroshi Ochiai

    bioRxiv   2023.11

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    DOI: 10.1101/2023.11.27.568629

  • Precise immunofluorescence canceling for highly multiplexed imaging capturing specific cell state

    Kosuke Tomimatsu, Takeru Fujii, Ryoma Bise, Kazufumi Hosoda, Yosuke Taniguchi, Hiroshi Ochiai, Hiroaki Ohishi, Kanta Ando, Ryoma Minami, Tachibana Taro, Kaori Tanaka, Seiichi Mori, Akihito Harada, Kazumitsu Maehara, Masao Nagasaki, Seiichi Uchida, Hiroshi Kimura, Masashi Narita, Yasuyuki Ohkawa

    bioRxiv   2023.10

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    Language:Others  

    DOI: 10.1101/2023.10.17.561810

  • Combined and differential roles of ADD domains of DNMT3A and DNMT3L on DNA methylation landscapes in mouse germ cells

    Naoki Kubo, Ryuji Uehara, Shuhei Uemura, Hiroaki Ohishi, Kenjiro Shirane, Hiroyuki Sasaki

    bioRxiv   2023.9

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    Language:Others  

    DOI: 10.1101/2023.09.07.556008

  • The DNMT3A ADD domain is required for efficient de novo DNA methylation and maternal imprinting in mouse oocytes Reviewed

    Ryuji Uehara, Wan Kin Au Yeung, Keisuke Toriyama, Hiroaki Ohishi, Naoki Kubo, Hidehiro Toh, Isao Suetake, Kenjiro Shirane, Hiroyuki Sasaki

    PLOS Genetics   19 ( 8 )   e1010855 - e1010855   2023.8

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    DOI: 10.1371/journal.pgen.1010855

  • Organization of transcription and 3D genome as revealed by live-cell imaging. Reviewed International journal

    Hiroshi Ochiai, Hiroaki Ohishi, Yuko Sato, Hiroshi Kimura

    Current opinion in structural biology   81   102615 - 102615   2023.5

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    DOI: 10.1016/j.sbi.2023.102615

  • STREAMING-Tag System: Technology to Enable Visualization of Transcriptional Activity and Subnuclear Localization of Specific Endogenous Genes. International journal

    Hiroaki Ohishi, Hiroshi Ochiai

    Methods in molecular biology (Clifton, N.J.)   2577   103 - 122   2023   ISSN:10643745

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    The Spliced TetO REpeAt, MS2 repeat, and INtein sandwiched reporter Gene tag (STREAMING-tag) system enables imaging of nuclear localization as well as the transcription activity of a specific endogenous gene at sub-100-nm resolution in living cells. The use of this system combined with imaging of epigenome states enables a detailed analysis of the impact of epigenome status on transcriptional dynamics. In this chapter, we describe a method for quantifying distances between Nanog gene and clusters of cofactor BRD4 using the STREAMING-tag system in mouse embryonic stem cells.

    DOI: 10.1007/978-1-0716-2724-2_8

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  • STREAMING-tag system reveals spatiotemporal relationships between transcriptional regulatory factors and transcriptional activity Reviewed

    Hiroaki Ohishi, Seiru Shimada, Satoshi Uchino, Jieru Li, Yuko Sato, Manabu Shintani, Hitoshi Owada, Yasuyuki Ohkawa, Alexandros Pertsinidis, Takashi Yamamoto, Hiroshi Kimura, Hiroshi Ochiai

    Nature Communications   2022.12

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    Language:Others   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41467-022-35286-2

  • STREAMING-tag system reveals spatiotemporal relationships between transcriptional regulatory factors and transcriptional activity

    Hiroaki Ohishi, Seiru Shimada, Satoshi Uchino, Jieru Li, Yuko Sato, Manabu Shintani, Hitoshi Owada, Yasuyuki Ohkawa, Alexandros Pertsinidis, Takashi Yamamoto, Hiroshi Kimura, Hiroshi Ochiai

    bioRxiv   2022.1

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    DOI: 10.1101/2022.01.06.472721

  • The DNMT3A PWWP domain is essential for the normal DNA methylation landscape in mouse somatic cells and oocytes. Reviewed International journal

    Kanako Kibe, Kenjiro Shirane, Hiroaki Ohishi, Shuhei Uemura, Hidehiro Toh, Hiroyuki Sasaki

    PLoS genetics   17 ( 5 )   e1009570   2021.5

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    DOI: 10.1371/journal.pgen.1009570

  • Ddhd1 knockout mouse as a model of locomotive and physiological abnormality in familial spastic paraplegia. Reviewed International journal

    Takuya Morikawa, Hiroaki Ohishi, Kengo Kosaka, Tomofumi Shimojo, Akihiro Nagano, Itsuki Taniguchi, Ryuta Fujioka, Kosei Moriyama, Motoko Unoki, Masatomo Takahashi, Motonao Nakao, Yoshihiro Izumi, Takeshi Bamba, Hiroyuki Sasaki, Shiroh Miura, Hiroki Shibata

    Bioscience reports   41 ( 2 )   2021.2

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1042/BSR20204171

  • Characterization of genetic-origin-dependent monoallelic expression in mouse embryonic stem cells. Reviewed International journal

    Hiroaki Ohishi, Wan Kin Au Yeung, Motoko Unoki, Kenji Ichiyanagi, Kei Fukuda, Shoji Maenohara, Kenjiro Shirane, Hatsune Chiba, Takashi Sado, Hiroyuki Sasaki

    Genes to cells : devoted to molecular & cellular mechanisms   25 ( 1 )   54 - 64   2020.1

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    DOI: 10.1111/gtc.12736

  • Poorly controlled diabetes during pregnancy and lactation activates the Foxo1 pathway and causes glucose intolerance in adult offspring. Reviewed International journal

    Yukihiro Inoguchi, Kenji Ichiyanagi, Hiroaki Ohishi, Yasutaka Maeda, Noriyuki Sonoda, Yoshihiro Ogawa, Toyoshi Inoguchi, Hiroyuki Sasaki

    Scientific reports   9 ( 1 )   10181 - 10181   2019.7

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41598-019-46638-2

  • Zfp281 Shapes the Transcriptome of Trophoblast Stem Cells and Is Essential for Placental Development. Reviewed International journal

    Takashi Ishiuchi, Hiroaki Ohishi, Tetsuya Sato, Satoshi Kamimura, Masayoshi Yorino, Shusaku Abe, Atsushi Suzuki, Teruhiko Wakayama, Mikita Suyama, Hiroyuki Sasaki

    Cell reports   27 ( 6 )   1742 - 1754   2019.5

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.celrep.2019.04.028

  • Role of UHRF1 in de novo DNA methylation in oocytes and maintenance methylation in preimplantation embryos. Reviewed International journal

    Shoji Maenohara, Motoko Unoki, Hidehiro Toh, Hiroaki Ohishi, Jafar Sharif, Haruhiko Koseki, Hiroyuki Sasaki

    PLoS genetics   13 ( 10 )   e1007042   2017.10

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    DOI: 10.1371/journal.pgen.1007042

  • Potential role for S100A4 in the disruption of the blood-brain barrier in collagen-induced arthritic mice, an animal model of rheumatoid arthritis. Reviewed International journal

    T Nishioku, K Furusho, A Tomita, H Ohishi, S Dohgu, H Shuto, A Yamauchi, Y Kataoka

    Neuroscience   189   286 - 92   2011.8

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.neuroscience.2011.05.044

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Books

  • イメージングによる空間配置情報を保持した1細胞トランスクリプトーム解析ーseqFISH+

    大石 裕晃

    羊土社  2020.12 

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    Responsible for pages:総ページ数:267p   Language:Japanese  

Presentations

  • 胚性幹細胞における単アリル性発現遺伝子はゲノム及び付随したエピゲノムによって制御される

    大石 裕晃, 鵜木 元香, 一柳 健司, 福田 渓, 白根 健次郎, 前之原 章司, 佐渡 敬, 佐々木 裕之

    生命科学系学会合同年次大会  2017.12 

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  • 胚性幹細胞における単アレル性発現遺伝子の由来とその転写制御

    大石 裕晃, 鵜木 元香, 福田 渓, 堀 恭平, 前之原 章司, 千葉 初音, 佐渡 敬, 佐々木 裕之

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集  2015.12 

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    Event date: 2015.12

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  • 胎児期および授乳期の血糖コントロール不良の母体糖尿病への暴露は仔の成長後の耐糖能と肝代謝に影響を与える

    井口 志洋, 一柳 健司, 大石 裕晃, 井口 登與志, 佐々木 裕之

    日本体質医学会雑誌  2019.2 

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    Event date: 2019.2

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  • 胎児期および授乳期の血糖コントロール不良の母体糖尿病への暴露は仔の成長後の耐糖能と肝代謝に影響を与える

    井口 志洋, 一柳 健司, 大石 裕晃, 井口 登與志, 佐々木 裕之

    日本体質医学会雑誌  2018.8 

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    Event date: 2018.8

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  • 血糖コントロール不良の母体糖尿病が仔の耐糖能異常および肝代謝にもたらす影響

    井口 志洋, 一柳 健司, 大石 裕晃, 前田 泰孝, 園田 紀之, 小川 佳宏, 井口 登與志, 佐々木 裕之

    日本臨床分子医学会学術総会プログラム・抄録集  2018.4 

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    Event date: 2018.4

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  • 血糖コントロール不良の母体糖尿病は仔の耐糖能異常および肝臓における代謝関連遺伝子の発現変化を性差をもって引き起こす

    井口 志洋, 一柳 健司, 大石 裕晃, 前田 泰孝, 園田 紀之, 小川 佳宏, 井口 登與志, 佐々木 裕之

    糖尿病  2018.4 

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  • 母体糖尿病が仔の表現型および遺伝子発現へ与える長期的な影響

    井口 志洋, 一柳 健司, 大石 裕晃, 前田 泰孝, 小川 佳宏, 井口 登與志, 佐々木 裕之

    生命科学系学会合同年次大会  2017.12 

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  • DDHD1の新規責任変異の同定とCRISPR/Cas9によるDdhd1ノックアウトマウスの作成

    森川 拓弥, 三浦 史郎, 大石 裕晃, 藤岡 竜太, 森山 耕成, 小坂 健悟, 下條 智史, 柴田 弘紀

    生命科学系学会合同年次大会  2017.12 

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  • マウス卵子のDNAメチル化確立におけるDnmt3aのADDドメインの役割の解明

    鳥山 敬祐, 白根 健次郎, 大石 裕晃, 佐々木 裕之

    生命科学系学会合同年次大会  2017.12 

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  • マウス卵子及び体細胞のDNAメチル化確立におけるDnmt3a PWWPドメインの役割

    木部 加奈子, 白根 健次郎, 大石 裕晃, 佐々木 裕之

    生命科学系学会合同年次大会  2017.12 

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  • 母体糖尿病が仔の表現型および遺伝子発現へ与える長期的な影響

    井口 志洋, 一柳 健司, 大石 裕晃, 前田 泰孝, 小川 佳宏, 井口 登與志, 佐々木 裕之

    日本内分泌学会雑誌  2017.4 

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  • 母体糖尿病が仔の表現型および遺伝子発現へ与える長期的な影響

    井口 志洋, 一柳 健司, 大石 裕晃, 前田 泰孝, 小川 佳宏, 井口 登與志, 佐々木 裕之

    糖尿病  2017.4 

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  • 原発性免疫不全症"ICF症候群"の原因遺伝子ZBTB24とCDCA7の機能解析

    伊藤 雄哉, 新田 洋久, 鵜木 元香, 大石 裕晃, Thijssen Peter E., Velasco Guillaume, 吉原 美奈子, 須山 幹太, Francastel Claire, Van Der Maarel Silvere M., 佐々木 裕之

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集  2015.12 

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    Event date: 2015.12

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  • Transcriptional regulation of monoallelically expressed genes in ground-state embryonic stem cells

    Hiroaki Ohishi, Motoko Unoki, Kei Fukuda, Shoji Maenohara, Kyohei Hori, Hatsune Chiba, Takashi Sado, Hiroyuki Sasaki

    GENES & GENETIC SYSTEMS  2015.12 

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    Country:Other  

  • 卵子形成過程および初期胚発生におけるUhrf1の重要性

    前之原 章司, 鵜木 元香, 小倉 淳郎, 井上 貴美子, 山縣 一夫, 堀 真由子, Sharif Jafar, 古関 明彦, 藤 英博, 大石 裕晃, 植田 幸嗣, 佐々木 裕之

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集  2015.12 

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    Event date: 2015.12

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  • Zfp57 is Essential for Transcriptional Regulation of Monoallelic Gene Expression in Ground-State Embryonic Stem Cells

    Hiroaki Ohishi, Motoko Unoki, Kei Fukuda, Takashi Sado, Hiroyuki Sasaki

    GENES & GENETIC SYSTEMS  2014.12 

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    Event date: 2014.12

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  • コラーゲン誘導関節炎マウスのパンヌスにおけるCyclophilin AとCD147の発現増加とその局在

    三浦 哲平, 西奥 剛, 大石 裕晃, 津曲 康輔, 山内 淳史, 首藤 英樹, 片岡 泰文

    日本薬学会年会要旨集  2011.3 

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    Event date: 2011.3

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  • 転写活性化状態における遺伝子周辺の粘性上昇がエンハンサーとプロモーターの接触時間を延長させる.

    大石裕晃, 新海創也, 大和田一志, 藤井健, 細田一史, 大浪修一, 山本卓, 大川恭行, 落合博

    第41 回染色体ワークショップ・第 22 回核ダイナミクス研究会  2024.1 

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    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Country:Japan  

  • 転写バーストにおける高次ゲノム構造と転写制御関連因子クラスターの空間的関係.

    大石裕晃、新海創也、大和田一志、大浪修一、山本卓、大川恭行、落合博

    第46回日本分子生物学会年会  2023.12 

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    Country:Japan  

  • STREAMING-tagによる転写活性と転写制御関連因子の時空間的な関連性の解明.

    大石 裕晃、島田 聖瑠、内野 哲志、Jieru Li、佐藤 優子、新谷 学文、大和田 一志、大川 恭行、Pertsinidis Alexandros、山本 卓、木村 宏、落合 博

    第75回日本細胞生物学会大会  2023.6 

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    Country:Japan  

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MISC

  • 特定RNA分子/DNA領域のライブイメージング技術

    大石 裕晃, 落合 博

    生体の科学   2023.6

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  • 【CRISPR最新ツールボックス 高効率・高精度なゲノム編集から遺伝子座の制御・検出まであなたの研究を拡張する!】CRISPR-Cas9システムによる特定遺伝子座ライブイメージング

    大石 裕晃, 落合 博

    実験医学   2021.5

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    CRISPR-Cas9システムを利用したゲノム編集技術は、基礎研究利用に留まらず、医療応用や、有用畜産物の作出など、広く革新をもたらしている。一方で、DNAを切断しないCas9変異体を用いることで、ゲノム編集とは異なる応用も可能である。その1つが、CRISPR-Cas9システムを利用した特定遺伝子座のライブイメージングである。本稿では、特定ゲノム領域の可視化の意義、CRISPR-Cas9による生細胞イメージングのツールボックス、さらに本技術を利用した応用研究を紹介し、今後の展望も踏まえて議論する。(著者抄録)

  • 【1細胞解析-技術と応用】技術 ライブイメージングによる1細胞動態解析

    大石 裕晃, 落合 博

    医学のあゆみ   2021.3

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    Language:Japanese  

    光学顕微鏡が普及し、肉眼では見えない細胞などの微細構造を観察できるようになり、多くの新しい生命現象の発見を支えてきた。とくに蛍光顕微鏡とその関連技術は、培養細胞のみならず、厚い組織切片、オルガノイド、生体などにおいて、特定分子の細胞内"動態"や発現量の"経時的変化"の測定を可能にし、創薬や病因同定などの医学分野にも深く関係している。本稿では、蛍光の原理および、1細胞レベルでのライブイメージングに用いられる蛍光顕微鏡、およびその派生技術である共焦点顕微鏡、多光子励起顕微鏡、ライトシート顕微鏡について解説する。さらに、1細胞レベルでの動態解析の重要性、蛍光ラベル化法、疾患オルガノイドを例にした医療への応用について解説する。(著者抄録)

  • Transcriptional regulation of monoallelically expressed genes in ground-state embryonic stem cells

    Hiroaki Ohishi, Motoko Unoki, Kei Fukuda, Shoji Maenohara, Kyohei Hori, Hatsune Chiba, Takashi Sado, Hiroyuki Sasaki

    GENES & GENETIC SYSTEMS   2015.12

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    Language:English  

  • Zfp57 is Essential for Transcriptional Regulation of Monoallelic Gene Expression in Ground-State Embryonic Stem Cells

    Hiroaki Ohishi, Motoko Unoki, Kei Fukuda, Takashi Sado, Hiroyuki Sasaki

    GENES & GENETIC SYSTEMS   2014.12

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    Language:English  

Professional Memberships

  • 日本分子生物学会

  • 日本細胞生物学会

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  • 日本ゲノム編集学会

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  • 日本エピジェネティクス研究会

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Research Projects

  • 蛍光イメージングによる時空間的なゲノムインプリンティング制御機構の解明

    Grant number:22K15084  2022 - 2024

    日本学術振興会  科学研究費助成事業  若手研究

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    Grant type:Scientific research funding

  • 新規KRAB-ZNF タンパク質によるエピジェネティック修飾の維持伝達機構の解明

    Grant number:14J03854  2014 - 2015

    日本学術振興会  科学研究費助成事業  若手研究

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    Grant type:Scientific research funding

  • ゲノムインプリンティングにおいてUHRF1が果たす役割の解明

    Grant number:24613005  2012 - 2014

    日本学術振興会  科学研究費助成事業  若手研究

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    Grant type:Scientific research funding