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Fundamental study of bone regeneration with site-specific epigenome editing

Research Project

Project/Area Number 17H04403
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionNagasaki University (2019-2021)
The University of Tokyo (2017-2018)

Principal Investigator

Ohba Shinsuke  長崎大学, 医歯薬学総合研究科(歯学系), 教授 (20466733)

Co-Investigator(Kenkyū-buntansha) 鄭 雄一  東京大学, 大学院工学系研究科(工学部), 教授 (30345053)
北條 宏徳  東京大学, 大学院医学系研究科(医学部), 准教授 (80788422)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2020: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Keywords再生医学 / 骨 / エピゲノム
Outline of Final Research Achievements

In this study, we first developed methods for generating skeletal cells, including osteoblasts, from human pluripotent stem cells (hPSCs). Gene expression profiling and open chromatin profiling in hPSC-derived endochondral bone tissues further identified cell-type-distinct gene expression profiles and open chromatin regions. Our datasets provide not only epigenome dynamics, but also enhancer regions that govern osteoblast differentiation during human skeletal development. Integrative analyses of the datasets, including cross-species analysis for conservation of target regions, will lead to identification of target enhancer regions for epigenome editing-mediated bone regeneration.

Academic Significance and Societal Importance of the Research Achievements

本研究は、「部位特異的エピゲノム編集による骨再生」という新しいアプローチに向けた基礎的知見の集積を目指したものである。マウス初代細胞における解析に加え、ヒト多能性幹細胞の骨芽細胞分化系を用いた解析を併用することで、ヒトの骨芽細胞分化におけるエピゲノム動態を、その遺伝子発現動態との関連も含めて明らかにした。取得されたエピゲノムデータは骨芽細胞分化を司るエンハンサー領域に関する情報を含んでいる。したがって、これらの領域は「部位特異的エピゲノム編集による骨再生」のための標的となりうると考えられる。

Report

(5 results)
  • 2021 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (56 results)

All 2022 2021 2020 2019 2018 2017 Other

All Int'l Joint Research (5 results) Journal Article (16 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 15 results,  Open Access: 12 results) Presentation (31 results) (of which Int'l Joint Research: 11 results,  Invited: 15 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] University of Connecticut Health Center(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] University of Connecticut Health Center/Stanford University(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of Connecticut Health Center/University of Southern California(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] University of Hong Kong(中国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] University of Connecticut Health Center(米国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] The Progress of Stem Cell Technology for Skeletal Regeneration2021

    • Author(s)
      Tani Shoichiro、Okada Hiroyuki、Chung Ung-il、Ohba Shinsuke、Hojo Hironori
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 3 Pages: 1404-1404

    • DOI

      10.3390/ijms22031404

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mesenchymal stromal cells in the bone marrow niche consist of multi-populations with distinct transcriptional and epigenetic properties2021

    • Author(s)
      Kanazawa Sanshiro、Okada Hiroyuki、Hojo Hironori、Ohba Shinsuke、Iwata Junichi、Komura Makoto、Hikita Atsuhiko、Hoshi Kazuto
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 15811-15811

    • DOI

      10.1038/s41598-021-94186-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gene regulatory landscape in osteoblast differentiation2020

    • Author(s)
      Hojo Hironori、Ohba Shinsuke
    • Journal Title

      Bone

      Volume: 137 Pages: 115458-115458

    • DOI

      10.1016/j.bone.2020.115458

    • NAID

      120006988169

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hedgehog Signaling in Skeletal Development: Roles of Indian Hedgehog and the Mode of Its Action.2020

    • Author(s)
      Ohba S.
    • Journal Title

      Int J Mol Sci

      Volume: 21(18) Issue: 18 Pages: 6665-6665

    • DOI

      10.3390/ijms21186665

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Understanding paraxial mesoderm development and sclerotome specification for skeletal repair2020

    • Author(s)
      Tani Shoichiro、Chung Ung-il、Ohba Shinsuke、Hojo Hironori
    • Journal Title

      Experimental & Molecular Medicine

      Volume: 52 Issue: 8 Pages: 1166-1177

    • DOI

      10.1038/s12276-020-0482-1

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hedgehog Activation Regulates Human Osteoblastogenesis2020

    • Author(s)
      Onodera Shoko、Saito Akiko、Hojo Hironori、Nakamura Takashi、Zujur Denise、Watanabe Katsuhito、Morita Nana、Hasegawa Daigo、Masaki Hideki、Nakauchi Hiromitsu、Nomura Takeshi、Shibahara Takahiko、Yamaguchi Akira、Chung Ung-il、Azuma Toshifumi、Ohba Shinsuke
    • Journal Title

      Stem Cell Reports

      Volume: 15 Issue: 1 Pages: 125-139

    • DOI

      10.1016/j.stemcr.2020.05.008

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stepwise strategy for generating osteoblasts from human pluripotent stem cells under fully defined xeno-free conditions with small-molecule inducers2020

    • Author(s)
      Zujur Denise、Kanke Kosuke、Onodera Shoko、Tani Shoichiro、Lai Jenny、Azuma Toshifumi、Xin Xiaonan、Lichtler Alexander C.、Rowe David W.、Saito Taku、Tanaka Sakae、Masaki Hideki、Nakauchi Hiromitsu、Chung Ung-il、Hojo Hironori、Ohba Shinsuke
    • Journal Title

      Regenerative Therapy

      Volume: 14 Pages: 19-31

    • DOI

      10.1016/j.reth.2019.12.010

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Simple and Robust Differentiation of Human Pluripotent Stem Cells toward Chondrocytes by Two Small-Molecule Compounds2019

    • Author(s)
      Kawata Manabu、Mori Daisuke、Kanke Kosuke、Hojo Hironori、Ohba Shinsuke、Chung Ung-il、Yano Fumiko、Masaki Hideki、Otsu Makoto、Nakauchi Hiromitsu、Tanaka Sakae、Saito Taku
    • Journal Title

      Stem Cell Reports

      Volume: 13 Issue: 3 Pages: 530-544

    • DOI

      10.1016/j.stemcr.2019.07.012

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Insights into Gene Regulatory Networks in Chondrocytes2019

    • Author(s)
      Hojo Hironori、Ohba Shinsuke
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 24 Pages: 6324-6324

    • DOI

      10.3390/ijms20246324

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ゲノムワイドデータとバイオインフォマティクスに基づく転写制御因子とゲノムDNAの相互作用分析2019

    • Author(s)
      大庭伸介, 北條宏徳
    • Journal Title

      バイオマテリアル-生体材料-

      Volume: 37 Pages: 244-251

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Synergistic co-regulation and competition by a SOX9-GLI-FOXA phasic transcriptional network coordinate chondrocyte differentiation transitions2018

    • Author(s)
      Tan Z, Niu B, Tsang KY, Melhado IG, Ohba S, He X, Huang Y, Wang C, McMahon AP, Jauch R, Chan D, Zhang MQ, Cheah KSE.
    • Journal Title

      PLOS Genetics

      Volume: 14 Issue: 4 Pages: e1007346-e1007346

    • DOI

      10.1371/journal.pgen.1007346

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fabrication of calcium phosphate-loaded carboxymethyl cellulose non-woven sheets for bone regeneration.2018

    • Author(s)
      Qi P, Ohba S, Hara Y, Fuke M, Ogawa T, Ohta S, Ito T
    • Journal Title

      Carbohydr Polym

      Volume: 189 Pages: 322-330

    • DOI

      10.1016/j.carbpol.2018.02.050

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bone regeneration by calcium phosphate-loaded carboxymethyl cellulose nonwoven sheets in canine femoral condyle defects.2018

    • Author(s)
      Sakamoto A, Qi P, Ohba S, Ohta S, Hara Y, Ogawa T, Tomokiyo M, Sasaki A, Takizawa H, Mochizuki M, Ito T, Honnami M
    • Journal Title

      Journal of biomedical materials research. Part B, Applied biomaterials.

      Volume: 印刷中 Issue: 5 Pages: 1516-1521

    • DOI

      10.1002/jbm.b.34243

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bone regeneration by human dental pulp stem cells using a helioxanthin derivative and cell-sheet technology.2018

    • Author(s)
      Fujii Y, Kawase-Koga Y, Hojo H, Yano F, Sato M, Chung UI, Ohba S, Chikazu D.
    • Journal Title

      Stem Cell Res Ther

      Volume: 9 Issue: 1 Pages: 24-24

    • DOI

      10.1186/s13287-018-0783-7

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Three-dimensional system enabling the maintenance and directed differentiation of pluripotent stem cells under defined conditions2017

    • Author(s)
      Zujur D, Kanke K, Lichtler AC, Hojo H, Chung UI, Ohba S
    • Journal Title

      Science Advanvces

      Volume: 3 Issue: 5

    • DOI

      10.1126/sciadv.1602875

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Improving chondrocyte hargests with poly(2-hydroxyethyl methacrylate) coated materials in the preparation for cartilage tissue engineering2017

    • Author(s)
      Harata M, Watanabe M, Nagata S, Ko EC, Ohba S, Takato T, Hikita A, Hoshi K
    • Journal Title

      Regenerative Therapy

      Volume: 7 Pages: 61-71

    • DOI

      10.1016/j.reth.2017.08.002

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Understanding skeletal development through single-cell analysis of human pluripotent stem cell-derived endochondral bone tissues.2022

    • Author(s)
      大庭伸介, 谷彰一郎, 岡田寛之, 鄭雄一, 北條宏徳
    • Organizer
      第127回日本解剖学会総会・全国学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 多能性幹細胞を用いた骨形成過程の再現2021

    • Author(s)
      大庭伸介
    • Organizer
      第75回日本口腔科学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] ヒト多能性幹細胞由来軟骨内骨化組織の作製2021

    • Author(s)
      大庭伸介
    • Organizer
      第63回歯科基礎医学会学術大会・総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Exploring human skeletal development using a human bone tissue induced from human pluripotent stem cells.2021

    • Author(s)
      Tani S, Okada H, Seki M, Suzuki Y, Saito T, Tanaka S, Chung UI, Hojo H, Ohba S
    • Organizer
      International Society for Stem Cell Research 2021 Annual Meeting
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Elucidating human skeletal development using single-cell analysis by inducing bone tissue formation from human pluripotent stem cells.2021

    • Author(s)
      Tani S, Okada H, Seki M, Suzuki Y, Saito T, Tanaka S, Chung UI, Hojo H, Ohba S
    • Organizer
      2021 Annual Meeting of the American Society for Bone and Mineral Research
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Elucidating human skeletal development by integrating single-cell analysis and bone tissue induction using human pluripotent stem cells.2021

    • Author(s)
      Tani S, Okada H, Seki M, Suzuki Y, Saito T, Tanaka S, Chung UI, Hojo H, Ohba S
    • Organizer
      ISSCR/JSRM International Symposium
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Elucidating human skeletal development by single-cell analyses with a model of endochondral bone formation using human pluripotent stem cells.2021

    • Author(s)
      Tani S, Okada H, Seki M, Suzuki Y, Saito T, Tanaka S, Chung UI, Hojo H, Ohba S
    • Organizer
      ESA (Endocrine Society of Australia)-SRB (Society for Reproductive Biology)-ANZBMS (Australian and New Zealand Bone and Mineral Society) 2021
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒト多能性幹細胞由来3次元骨組織誘導法と単一細胞解析を用いたヒト骨形成機構の探索2021

    • Author(s)
      谷彰一郎, 岡田寛之, 齋藤琢, 田中栄, 鄭雄一, 北條宏徳, 大庭伸介
    • Organizer
      第39回日本骨代謝学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ヒト多能性幹細胞を用いたヒト骨形成過程の再現と応用2021

    • Author(s)
      谷彰一郎, 岡田寛之, 関真秀, 鈴木穣, 斎藤琢, 田中栄, 鄭雄一, 北條宏徳, 大庭伸介
    • Organizer
      第36回日本整形外科学会基礎集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ヒト多能性幹細胞由来の3次元骨組織誘導とシングルセル・マルチオーム解析を用いたヒト骨形成機構の解明2021

    • Author(s)
      谷彰一郎, 岡田寛之, 関真秀, 鈴木穣, 斎藤琢, 田中栄, 鄭雄一, 北條宏徳, 大庭伸介
    • Organizer
      第44回日本分子生物学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Generation of skeletal cells from pluripotent stem cells.2020

    • Author(s)
      Shinsuke Ohba
    • Organizer
      The 68th Meeting of Japanese Association for Dental Research
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 骨軟骨形成機構の理解に向けて2020

    • Author(s)
      大庭伸介
    • Organizer
      第62回日本顕微鏡学会九州支部集会・学術講演会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 骨・軟骨の形成における遺伝子発現制御機構の探索.2020

    • Author(s)
      大庭伸介
    • Organizer
      第125回日本解剖学会総会・全国学術集会(誌上開催)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 多能性幹細胞由来の骨形成性細胞の作製と応用.2019

    • Author(s)
      大庭伸介
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 骨・軟骨発生の理解と多能性幹細胞を用いた発生過程の再現.2019

    • Author(s)
      大庭伸介
    • Organizer
      日本解剖学会第75回九州支部学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] マウス脛骨骨折モデルにおける可溶型Frizzled2による骨折治癒促進.2019

    • Author(s)
      中島健太, 北浦義昭, 長谷川尚, 山崎雄二, 長尾研二, 鄭雄一, 大庭伸介
    • Organizer
      第37回日本骨代謝学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Runx2は骨格発生において細胞種特異的な転写制御領域に作用する.2019

    • Author(s)
      北條宏徳, 山川晃, 齋藤琢, 小野寺晶子, 東俊文, 鄭雄一, 大庭伸介
    • Organizer
      第37回日本骨代謝学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Local administration of soluble Frizzled2 accelerate bony callus formation during bone fracture repair process in a mouse model.2019

    • Author(s)
      Nakajima K, Kitaura Y, Hasegawa H, Yamazaki Y, Nagao K, Chung UI, Ohba S
    • Organizer
      American Society for Bone and Mineral Research
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cell-type disctinct Runx2 regulatory action underlies its distinct functions in osteoblast and chondrocytes.2019

    • Author(s)
      Hojo H, Ohba S, Yamakawa A, Guo Q, He X, Saito T, Onodera S, Azuma T, Chung UI, McMahon AP
    • Organizer
      American Society for Bone and Mineral Research
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Exploring the gene regulatory landscape in skeletal cells.2019

    • Author(s)
      Shinsuke Ohba
    • Organizer
      2019 Gordon Research Conference Cartilage Biology & Pathology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A chondrocyte-specifc Indian hedgehog enhancer as an OA-driving enhancer2019

    • Author(s)
      Akira Yamakawa, Hironori Hojo, Ung-il Chung, Shinsuke Ohba
    • Organizer
      Orthopaedic Research Society (ORS) 2019 Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 多能性幹細胞の分化システムとChIP-seqを駆使して骨芽細胞分化における転写制御を理解する2018

    • Author(s)
      大庭伸介
    • Organizer
      第60回歯科基礎医学会学術大会・総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 次世代シークエンサーを用いた骨格系細胞における遺伝子発現制御機構の解析2018

    • Author(s)
      大庭伸介
    • Organizer
      第60回歯科基礎医学会学術大会・総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 多能性幹細胞を用いた骨芽細胞分化のインビトロモデリングと分化機序解析への応用2018

    • Author(s)
      大庭伸介
    • Organizer
      第4回日本筋学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 骨再生療法・基礎的観点から2018

    • Author(s)
      大庭伸介
    • Organizer
      第36回日本骨代謝学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Identification of a chondrocyte-specific Indian hedgehog enhancer and Sox9-mediated mechanisms of the enhancer activation2018

    • Author(s)
      Akira Yamakawa, Hironori Hojo, Ung-il Chung, Shinsuke Ohba
    • Organizer
      2018 OARSI World Congress on Osteoarthritis
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 軟骨細胞特異的なIndian hedgehogのエンハンサーの同定とSox9による活性化機構2018

    • Author(s)
      山川晃, 北條宏徳, 鄭雄一, 大庭伸介
    • Organizer
      第33回日本整形外科学会基礎学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 骨格形成における遺伝子発現機構をゲノムスケールで理解する.2018

    • Author(s)
      大庭伸介
    • Organizer
      第17回日本再生医療学会総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Modeling of bone remodeling by three-dimensional co-culture of mouse embryonic stem cell-derived osteoblasts and osteoclast precursors.2017

    • Author(s)
      Zujur DC, Hikita A, Kanke K, Hojo H, Chung UI, Ohba S
    • Organizer
      International Society for Stem Cell Research 15th Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] In vivo bone formation by osteoblasts generated from human induced pluripotent stem cells under fully defined xeno-free conditions.2017

    • Author(s)
      Zujur DC, Kanke K, Hojo H, Onodera S, Azuma T, Chung UI, Ohba S
    • Organizer
      39th Annual Meeting of the American Society for Bone and Mineral Research
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Genome-scale understanding of gene regulatory landscape in skeletal cells.2017

    • Author(s)
      Shinsuke Ohba
    • Organizer
      14th Bone Biology Forum
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Remarks] researchmap

    • URL

      https://researchmap.jp/shin-o

    • Related Report
      2020 Annual Research Report
  • [Remarks] 長崎大学大学院医歯薬学総合研究科細胞生物学分野

    • URL

      http://www.de.nagasaki-u.ac.jp/dokuji/kaibou-2/

    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 椎板細胞の製造方法および該椎板細胞の利用2022

    • Inventor(s)
      大庭伸介、谷彰一郎、北條宏徳、鄭雄一
    • Industrial Property Rights Holder
      大庭伸介、谷彰一郎、北條宏徳、鄭雄一
    • Industrial Property Rights Type
      特許
    • Filing Date
      2022
    • Related Report
      2020 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 椎板細胞の製造方法および該椎板細胞の利用2021

    • Inventor(s)
      大庭伸介、谷彰一郎、北條宏徳、鄭雄一
    • Industrial Property Rights Holder
      大庭伸介、谷彰一郎、北條宏徳、鄭雄一
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-041384
    • Filing Date
      2021
    • Related Report
      2020 Annual Research Report

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Published: 2017-04-28   Modified: 2023-01-30  

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