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Molecular understanding of the accumulation of mesenchymal stem cells in vivo by photo-manipulation techniques and its application to bone-related diseases

Research Project

Project/Area Number 17H04399
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Dental engineering/Regenerative dentistry
Research InstitutionOkayama University

Principal Investigator

Takarada Takeshi  岡山大学, 医歯薬学総合研究科, 教授 (30377428)

Co-Investigator(Kenkyū-buntansha) 窪木 拓男  岡山大学, 医歯薬学総合研究科, 教授 (00225195)
大野 充昭  岡山大学, 医歯薬学総合研究科, 准教授 (60613156)
佐藤 守俊  東京大学, 大学院総合文化研究科, 教授 (00323501)
戸村 道夫  大阪大谷大学, 薬学部, 教授 (30314321)
戸口田 淳也  京都大学, ウイルス・再生医科学研究所, 教授 (40273502)
渡辺 亮  京都大学, iPS細胞研究所, 特定拠点助教 (60506765)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2020: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Keywords光操作 / 遺伝子改変マウス / 間葉系幹細胞 / 光操作技術 / 幹細胞
Outline of Final Research Achievements

In this study, we generated a tTA-dependent photoactivatable Cre-loxP recombinase knock-in mouse model (TRE-PA-Cre mice) using a CRISPR/Cas9 system. These mice were crossed with ROSA26-tdTomato mice (Cre reporter mouse) to visualize DNA recombination as marked by tdTomato expression. We demonstrated that external noninvasive LED blue light illumination allows efficient DNA recombination in the liver of TRE-PA-Cre:ROSA26-tdTomato mice transfected with tTA expression vectors using hydrodynamic tail vein injection. The TRE-PA-Cre mouse established here promises to be useful for optogenetic genome engineering in a noninvasive, spatiotemporal, and cell-type specific manner in vivo.

Academic Significance and Societal Importance of the Research Achievements

従来不可能であった「時間・空間(光照射時/部位)特異的」な精度を持つ生体内遺伝子操作が可能となり、今後、様々な組織・細胞で生物医学研究の新規戦略手法として幅広く使用されることが期待される。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (27 results)

All 2021 2020 2019 2018 2017 Other

All Int'l Joint Research (3 results) Journal Article (17 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 17 results,  Open Access: 9 results) Presentation (7 results) (of which Invited: 6 results)

  • [Int'l Joint Research] University of Rochester Medical Center(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Monash University(オーストラリア)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] University of Rochester Medical Center(米国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] PRRX1 promotes malignant properties in human osteosarcoma2021

    • Author(s)
      Joko Ryoji、Yamada Daisuke、Nakamura Masahiro、Yoshida Aki、Takihira Shota、Takao Tomoka、Lu Ming、Sato Kohei、Ito Tatsuo、Kunisada Toshiyuki、Nakata Eiji、Ozaki Toshifumi、Takarada Takeshi
    • Journal Title

      Translational Oncology

      Volume: 14 Issue: 1 Pages: 100960-100960

    • DOI

      10.1016/j.tranon.2020.100960

    • NAID

      120007004820

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] RUNX2 regulates leukemic cell metabolism and chemotaxis in high-risk T cell acute lymphoblastic leukemia2021

    • Author(s)
      Matthijssens Filip、Sharma Nitesh D.、Takarada Takeshi、et al.
    • Journal Title

      Journal of Clinical Investigation

      Volume: 131 Issue: 6

    • DOI

      10.1172/jci141566

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] BMP-2/β-TCP Local Delivery for Bone Regeneration in MRONJ-Like Mouse Model2020

    • Author(s)
      Mikai Akihiro、Ono Mitsuaki、Tosa Ikue、Nguyen Ha Thi Thu、Hara Emilio Satoshi、Nosho Shuji、Kimura-Ono Aya、Nawachi Kumiko、Takarada Takeshi、Kuboki Takuo、Oohashi Toshitaka
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 19 Pages: 7028-7028

    • DOI

      10.3390/ijms21197028

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Core Binding Factors are essential for ovulation, luteinization, and female fertility in mice2020

    • Author(s)
      Lee-Thacker Somang、Jeon Hayce、Choi Yohan、Taniuchi Ichiro、Takarada Takeshi、Yoneda Yukio、Ko CheMyong、Jo Misung
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 9921-9921

    • DOI

      10.1038/s41598-020-64257-0

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A RUNX2 stabilization pathway mediates physiologic and pathologic bone formation2020

    • Author(s)
      Kim Jung-Min、Yang Yeon-Suk、Park Kwang Hwan、Ge Xianpeng、Xu Ren、Li Na、Song Minkyung、Chun Hyunho、Bok Seoyeon、Charles Julia F.、Filhol-Cochet Odile、Boldyreff Brigitte、Dinter Teresa、Yu Paul B.、Kon Ning、Gu Wei、Takarada Takeshi、Greenblatt Matthew B.、Shim Jae-Hyuck
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1 Pages: 2289-2289

    • DOI

      10.1038/s41467-020-16038-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Establishment of a tTA-dependent photoactiveatable Cre recombinease knock-in mouse model for optogenetic genome engineering.2020

    • Author(s)
      9.Takao, T., Hiraoka, Y., Kawabe, K., Yamada, D., Ming, L., Tanaka, K., Sato, M., Takarada, T.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 526 Issue: 1 Pages: 213-217

    • DOI

      10.1016/j.bbrc.2020.03.015

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Inhibition of the glutamine transporter SNAT1 confers neuroprotection in mice by modulating the mTOR-autophagy system2019

    • Author(s)
      Yamada Daisuke、Kawabe Kenji、Tosa Ikue、Tsukamoto Shunpei、Nakazato Ryota、Kou Miki、Fujikawa Koichi、Nakamura Saki、Ono Mitsuaki、Oohashi Toshitaka、Kaneko Mari、Go Shioi、Hinoi Eiichi、Yoneda Yukio、Takarada Takeshi
    • Journal Title

      Communications Biology

      Volume: 2 Issue: 1

    • DOI

      10.1038/s42003-019-0582-4

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glutamatergic neurons in the medial prefrontal cortex mediate the formation and retrieval of cocaine-associated memories in mice2019

    • Author(s)
      Zhang Tong、Yanagida Junko、Kamii Hironori、Wada Shintaro、Domoto Masaki、Sasase Hitoki、Deyama Satoshi、Takarada Takeshi、Hinoi Eiichi、Sakimura Kenji、Yamanaka Akihiro、Maejima Takashi、Mieda Michihiro、Sakurai Takeshi、Nishitani Naoya、Nagayasu Kazuki、Kaneko Shuji、Minami Masabumi、Kaneda Katsuyuki
    • Journal Title

      Addiction Biology

      Volume: 印刷中 Issue: 1 Pages: 1-11

    • DOI

      10.1111/adb.12723

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Postnatal Runx2 deletion leads to low bone mass and adipocyte accumulation in mice bone tissues2019

    • Author(s)
      Tosa Ikue、Yamada Daisuke、Yasumatsu Misa、Hinoi Eiichi、Ono Mitsuaki、Oohashi Toshitaka、Kuboki Takuo、Takarada Takeshi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 516 Issue: 4 Pages: 1229-1233

    • DOI

      10.1016/j.bbrc.2019.07.014

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Type IV collagen α6 chain is a regulator of keratin 10 in keratinization of oral mucosal epithelium2018

    • Author(s)
      Komori T, Ono M, Hara ES, Ueda J, Nguyen HTT, Nguyen HT, Yonezawa T, Maeba T, Ono A, Takarada T, Momota R, Maekawa K, Kuboki T, Oohashi T
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 2612-2612

    • DOI

      10.1038/s41598-018-21000-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Core Binding Factor β Expression in Ovarian Granulosa Cells Is Essential for Female Fertility.2018

    • Author(s)
      Lee-Thacker S, Choi Y, Taniuchi I, Takarada T, Yoneda Y, Ko C, Jo M.
    • Journal Title

      Endocrinology.

      Volume: 159 Issue: 5 Pages: 2094-2109

    • DOI

      10.1210/en.2018-00011

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The MAPK Erk5 is necessary for proper skeletogenesis involving a Smurf-Smad-Sox9 molecular axis.2018

    • Author(s)
      Iezaki T, Fukasawa K, Horie T, Park G, Robinson S, Nakaya M, Fujita H, Onishi Y, Ozaki K, Kanayama T, Hiraiwa M, Kitaguchi Y, Kaneda K, Yoneda Y, Takarada T, Guo XE, Kurose H, Hinoi E.
    • Journal Title

      Development

      Volume: 145 Issue: 14 Pages: 164004-164004

    • DOI

      10.1242/dev.164004

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Radiobrominated benzimidazole-quinoline derivatives as Platelet-derived growth factor receptor beta (PDGFRβ) imaging probes.2018

    • Author(s)
      Effendi N, Mishiro K, Takarada T, Makino A, Yamada D, Kitamura Y, Shiba K, Kiyono Y, Odani A, Ogawa K.
    • Journal Title

      Sci Rep.

      Volume: 8 Issue: 1 Pages: 10369-10369

    • DOI

      10.1038/s41598-018-28529-0

    • NAID

      120007185660

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Physiological role of urothelial cancer-associated one long noncoding RNA in human skeletogenic cell differentiation2017

    • Author(s)
      Ishikawa T, Nishida T, Ono M, Takarada T, Nguyen HT, Kurihara S, Furumatsu T, Murase Y, Takigawa M, Oohashi T, Kamioka H, Kubota S
    • Journal Title

      J Cell. Physiol.

      Volume: 233(6) Issue: 6 Pages: 4825-4840

    • DOI

      10.1002/jcp.26285

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bone Resorption Is Regulated by Circadian Clock in Osteoblasts.2017

    • Author(s)
      Takarada T, Xu C, Ochi H, Nakazato R, Yamada D, Nakamura S, Kodama A, Shimba S, Mieda M, Fukasawa K, Ozaki K, Iezaki T, Fujikawa K, Yoneda Y, Numano R, Hida A, Tei H, Takeda S, Hinoi E.
    • Journal Title

      J Bone Miner Res.

      Volume: 32 Issue: 4 Pages: 872-881

    • DOI

      10.1002/jbmr.3053

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deletion of Runx2 in Articular Chondrocytes Decelerates the Progression of DMM-Induced Osteoarthritis in Adult Mice2017

    • Author(s)
      Liao Lifan、Zhang Shanxing、Gu Jianhong、Takarada Takeshi、Yoneda Yukio、Huang Jian、Zhao Lan、Oh Chun-do、Li Jun、Wang Baoli、Wang Meiqing、Chen Di
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 2371-2371

    • DOI

      10.1038/s41598-017-02490-w

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The transcriptional modulator Ifrd1 controls PGC-1α expression under short-term adrenergic stimulation in brown adipocytes2017

    • Author(s)
      Park Gyujin、Horie Tetsuhiro、Kanayama Takashi、Fukasawa Kazuya、Iezaki Takashi、Onishi Yuki、Ozaki Kakeru、Nakamura Yukari、Yoneda Yukio、Takarada Takeshi、Hinoi Eiichi
    • Journal Title

      The FEBS Journal

      Volume: 284 Issue: 5 Pages: 784-795

    • DOI

      10.1111/febs.14019

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] 組織機能修復・再生・創薬を指向した間葉系幹細胞の幹細胞の階層性/系譜の分子理解2018

    • Author(s)
      宝田 剛志
    • Organizer
      第29回創薬・薬理フォーラム岡山
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Dissecting the hierarchy and lineage of mesenchymal stem cells by mouse genetics.2018

    • Author(s)
      Takeshi Takarada
    • Organizer
      International Symposium on Immunology and Tissue Regeneration in Okayama / 12th URA International Symposium
    • Related Report
      2018 Annual Research Report
  • [Presentation] 間葉系幹細胞の階層性・系譜の分子理解と応用2017

    • Author(s)
      宝田 剛志
    • Organizer
      第26回硬組織再生生物学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 間葉系幹細胞の階層性・系譜の分子理解と骨疾患への応用2017

    • Author(s)
      宝田 剛志
    • Organizer
      第54回ネフロンフォーラム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 骨格形成過程における細胞集団不均一性の理解2017

    • Author(s)
      宝田 剛志
    • Organizer
      第5回細胞凝集研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 骨組織再生材料開発を指向した骨格形成過程の階層性・系譜の分子理解2017

    • Author(s)
      宝田 剛志
    • Organizer
      日本バイオマテリアル学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 生体内での間葉系幹細胞系譜の分子理解と、その応用2017

    • Author(s)
      宝田 剛志
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
    • Invited

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Published: 2017-04-28   Modified: 2022-01-27  

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