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特命准教授 |
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- 特命准教授 |
From School 【 display / non-display 】
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Tokyo University of Science Faculty of Science and Engineering Graduated
1998 - 2002
From Graduate School 【 display / non-display 】
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Tokyo University of Science Graduate School, Division of Science and Engineering Doctor Course Completed
2004 - 2007
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Tokyo University of Science Graduate School, Division of Science and Engineering Master Course Completed
2002 - 2004
Studying abroad experiences 【 display / non-display 】
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2010.10 - 2015.05 Cell Biology Department, Duke University Postdoctoral fellow
Employment Record in Research 【 display / non-display 】
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Tokyo University of Agriculture Genome Research Center 特命准教授
2025.04
External Career 【 display / non-display 】
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Tokyo University of Agriculture NODAI Genome Research Center Specially Appointed Associate Professor
2025.04
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Yokohama City University School of Medicine Medical Course , Regenerative Medicine Assistant Professor
2015.06 - 2025.03
Professional Memberships 【 display / non-display 】
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日本生理学会
2017.07
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日本生化学会
2004.09
Research Areas 【 display / non-display 】
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Life Science / Anatomy
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Life Science / Cell biology
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Life Science / Developmental biology
Research Interests 【 display / non-display 】
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血管付与オルガノイド
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肝臓オルガノイド
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気道上皮
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幹細胞生物学
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宇宙実験
Papers 【 display / non-display 】
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Human iPSC–liver organoid transplantation reduces fibrosis through immunomodulation
Tomomi Tadokoro, Soichiro Murata, Mimoko Kato, Yasuharu Ueno, Tomonori Tsuchida, Ayumu Okumura, Yoshiki Kuse, Takahiro Konno, Yutaro Uchida, Yuriko Yamakawa, Marina Zushi, Megumi Yajima, Tatsuya Kobayashi, Shunsuke Hasegawa, Yumi Kawakatsu-Hatada, Yoshihito Hayashi, Shun Osakabe, Takuji Maeda, Kodai Kimura, Akihiro Mori, Maiko Tanaka, Yu Kamishibahara, Megumi Matsuo, Yun-Zhong Nie, Satoshi Okamoto, Takayoshi Oba, Naoki Tanimizu, Hideki Taniguchi
Science Translational Medicine 16 ( 757 ) 2024.07
Authorship：Lead author, Corresponding author Publishing type：Research paper (scientific journal) Publisher：American Association for the Advancement of Science (AAAS)
Donor organ shortages for transplantation remain a serious global concern, and alternative treatment is in high demand. Fetal cells and tissues have considerable therapeutic potential as, for example, organoid technology that uses human induced pluripotent stem cells (hiPSCs) to generate unlimited human fetal-like cells and tissues. We previously reported the in vivo vascularization of early fetal liver–like hiPSC-derived liver buds (LBs) and subsquent improved survival of recipient mice with subacute liver failure. Here, we show hiPSC–liver organoids (LOs) that recapitulate midgestational fetal liver promote de novo liver generation when grafted onto the surface of host livers in chemical fibrosis models, thereby recovering liver function. We found that fetal liver, a hematopoietic tissue, highly expressed macrophage-recruiting factors and antifibrotic M2 macrophage polarization factors compared with the adult liver, resulting in fibrosis reduction because of CD163 <sup>+</sup> M2-macrophage polarization. Next, we created midgestational fetal liver–like hiPSC-LOs by fusion of hiPSC-LBs to induce static cell-cell interactions and found that these contained complex structures such as hepatocytes, vasculature, and bile ducts after transplantation. This fusion allowed the generation of a large human tissue suitable for transplantation into immunodeficient rodent models of liver fibrosis. hiPSC-LOs showed superior liver function compared with hiPSC-LBs and improved survival and liver function upon transplantation. In addition, hiPSC-LO transplantation ameliorated chemically induced liver fibrosis, a symptom of liver cirrhosis that leads to organ dysfunction, through immunomodulatory effects, particularly on CD163 <sup>+</sup> phagocytic M2-macrophage polarization. Together, our results suggest hiPSC-LO transplantation as a promising therapeutic option for liver fibrosis.
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BMP signaling and cellular dynamics during regeneration of airway epithelium from basal progenitors. Reviewed International coauthorship International journal
Tadokoro, T., Gao, X., Hong, C.C., Hotten, D., and Hogan, B.L.
Development 143 764 - 773 2016.03
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
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IL-6/STAT3 promotes regeneration of airway ciliated cells from basal progenitors. Reviewed International coauthorship International journal
Tadokoro, T., Wang, Y., Barak, L., Bai, Y., Randell, S.H., and Hogan, B.L.
Proceedings of the National Academy of Sciences of the United States of America 111 ( 35 ) E3641 - E3649 2014.07
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
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Placenta-derived factors contribute to human iPSC-liver organoid growth. International journal
Yoshiki Kuse, Shinya Matsumoto, Syusaku Tsuzuki, Erica Carolina, Takashi Okumura, Toshiharu Kasai, Soichiro Yamabe, Kiyoshi Yamaguchi, Yoichi Furukawa, Tomomi Tadokoro, Yasuharu Ueno, Takayoshi Oba, Naoki Tanimizu, Hideki Taniguchi
Nature communications 16 ( 1 ) 2493 - 2493 2025.03
Language：English Publishing type：Research paper (scientific journal)
Organoids derived from human induced pluripotent stem cells (hiPSC) are potentially applicable for regenerative medicine. However, the applications have been hampered by limited organoid size and function as a consequence of a lack of progenitor expansion. Here, we report the recapitulation of progenitor expansion in hiPSC-liver organoids based on the analysis of mouse development. Visualization of blood perfusion and oxygen levels in mouse embryos reveals a transient hypoxic environment during hepatoblast expansion, despite active blood flow. During this specific stage, the placenta expresses various growth factors. Human and mouse placenta-liver interaction analysis identifies various placenta-derived factors. Among them, IL1α efficiently induces the growth in hiPSC-liver organoids as well as mouse fetal livers following progenitor expansion under hypoxia. Furthermore, subsequent oxygenation demonstrates that progenitors expanded by IL1α contribute to hiPSC-liver organoid size and function. Taken together, we demonstrate that treatment with the placenta-derived factor under hypoxia is a crucial human organoid culture technique that efficiently induces progenitor expansion.
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Optimizing cell migration assays: Critical roles of fluorescent labeling and chemoattractant gradients. Reviewed International journal
Tomomi Tadokoro, Mimoko Kato, Tatsuya Kobayashi, Hideki Taniguchi
Biochemical and biophysical research communications 739 150998 - 150998 2024.11
Authorship：Lead author, Corresponding author Language：English Publishing type：Research paper (scientific journal)
Cell migration assays, also known as chemotaxis assays, are widely used to measure the migratory capacities of cancer cells, leukocytes, macrophages, and other motile cell types. In these assays, fluorescently labeled cells are seeded onto cell culture inserts with microporous membranes that block light transmission from 490 to 700 nm. The migrated cells are then observed and quantified from the bottom of the microporous membrane using a fluorescence microscope. In this study, we conducted cell migration assays using macrophages as the motile cells. We discovered that the commonly employed fluorescent labeling method using calcein acetoxymethyl ester (calcein AM) can lead to the time-dependent attenuation of fluorescent signals in certain cell types during migration assays, potentially compromising assay stability. This study overcame this limitation by utilizing PKH26, which fluorescently labels cell surfaces through a mechanism distinct from that of calcein AM. With this modification, we observed a consistent increase in the number of migrating macrophages over time. We also demonstrated that the gradient of chemoattractants is key to the success of cell migration assays. Our improved protocol provided reliable and stable results for cell migration assays.
Books and Other Publications 【 display / non-display 】
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オルガノイド研究 Reviewed
田所 友美（ Role： Joint author , iPS細胞オルガノイドを活用したヒト臓器の創出に向けた技術開発）
(株)エヌ・ティー・エス 2024.08
Total pages：405 Responsible for pages：5 Language：Japanese Book type：Scholarly book
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オルガノイド研究 Reviewed
田所 友美（ Role： Joint author , 肺オルガノイド研究の潮流と再生医療への応用）
(株)エヌ・ティー・エス 2024.08
Total pages：405 Responsible for pages：7 Language：Japanese Book type：Scholarly book
最近15年ほどの間に急速な発展を遂げてきたオルガノイド研究について、日本のオルガノイド研究に携わる研究者が寄稿した本である。肺オルガノイドの現在までの進展についてまとめた著書である。
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Advances in Liver Organoid Technology and Beyond.
Tadokoro, T. and Taniguchi, H.（ Role： Joint author）
Advances in Medicine and Biology. 2019.11
Total pages：273 Responsible for pages：26 Language：English Book type：Scholarly book
Misc 【 display / non-display 】
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留学先の選び方
田所 友美
実験医学オンライン留学のすゝめ！ 2015.07
Authorship：Corresponding author Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)
Industrial Property Rights 【 display / non-display 】
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細胞塊融合法
谷口 英樹, 田所 友美
Application no：特願2018-61095 Date applied：2018.03
Patent/Registration no：特許第7228269号 Date registered：2023.02
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CONSTRUCT HAVING STRUCTURE AND CELL MASS LINKED TOGETHER
Hideki Taniguchi, Tomomi Tadokoro
Applicant：Yokohama City University
Application no：特願2017-208853 Date applied：2017.10
Patent/Registration no：特許第7158040号 Date registered：2022.10
Country of applicant：Domestic , International (PCT) application Country of acquisition：Domestic
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細胞塊を集合させる方法及び細胞塊を集合させる装置
谷口 英樹、田所 友美、東端 晃、坂下 哲也
Applicant：公立大学法人横浜市立大学
Application no：特願2017-230609 Date applied：2017.11
Patent/Registration no：特許第7158040号 Date registered：2022.10
Country of applicant：Domestic , International (PCT) application Country of acquisition：Domestic
Honours, Awards and Prizes 【 display / non-display 】
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Travel Grants for Postdoctoral Researchers in Overseas
2013.12 日本分子生物学会
田所 友美
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川口基金トラベルグラント
2005.09 川口基金
田所 友美
Scientific Research Funds Acquisition Results 【 display / non-display 】
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気道上皮細胞による気道軟骨/平滑筋の恒常性維持機構の解明
Grant number：21K08208 2021.04 - 2024.03
日本学術振興会 科学研究費助成事業 基盤研究(C) 基盤研究(C)
田所 友美
Authorship：Principal investigator
Grant amount：\4160000 （ Direct Cost: \3200000 、 Indirect Cost：\960000 ）
哺乳類の呼吸器系は、細菌やウィルスを取り除き空気を運ぶ気道と酸素を取り込む肺胞から成る。気道の内側は気道上皮細胞に覆われており、異物を捉える粘液を分泌する杯細胞を含む分泌細胞とそれらを排出する繊毛細胞から構成され、その下に気道上皮幹細胞である基底細胞が存在する。一方、気道の外側は軟骨と平滑筋が組み合わさり、管の強度を保つと同時に管の太さを調節可能な構造になっている。腹側背側の気道上皮幹細胞において遺伝子発現に大きな相違があることについて国際学術誌に発表を行い、気道の発生や維持機構に気道上皮幹細胞のヘテロジェネイティが果たす役割を示唆している（Tadokoro et al., Biol Open, 2021）。抽出された遺伝子を気道上皮特異的にノックアウトし、気道の形成、特に気道軟骨や気道平滑筋形成にどのような影響を与えるかについて検討を行う予定である。本年度はまずゲノム編集技術を使用した遺伝子改変floxマウスの作製に取り組み、仔を得た（理化学研究所との共同研究）。並行してマウス気道上皮と気道軟骨、気道平滑筋の共培養系を試みたが、各々の細胞系譜の至適培養条件に相違が認められた。ヒトiPS細胞からの平滑筋分化培養法について検討を行い、平滑筋マーカーであるTaglnやSMAなどの発現を確認した。ヒトiPS細胞からの軟骨分化についても軟骨マーカーであるColIIなどの発現が確認された。気道間葉系細胞と気道上皮細胞の共培養系についての検討を実施し、軟骨細胞と他の細胞の至適培養条件が異なることが明らかとなった。
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3D tissue reconstruction with hierarchical vascular networks
2020.04 - 2023.03
Japan Agency for Medical Research and Development
Yoshiki Kuse, Keisuke Tanaka, Yuko Yamamoto
Authorship：Principal investigator
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in vitro血管発生再現法を用いた肺組織再構成
2019.04 - 2021.03
日本学術振興会 挑戦的研究（萌芽）
田所 友美
Authorship：Principal investigator Grant type：Competitive
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移植医療に貢献可能なiPS細胞オルガノイドを駆使したヒト臓器創出技術の開発
Grant number：24H00641 2024.04 - 2027.03
日本学術振興会 科学研究費助成事業 基盤研究(A)
谷口 英樹, 谷水 直樹, 奥村 高志, 田所 友美, 上野 康晴, 久世 祥己
Grant amount：\48230000 （ Direct Cost: \37100000 、 Indirect Cost：\11130000 ）
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Development of human organ generation technology recapitulating microgravity environment
Grant number：23K11806 2023.04 - 2026.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）
Other External Funds 【 display / non-display 】
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回転求心培養法による多階層血管構造を有するヒト臓器の創出
2022.04 - 2023.03
一般財団法人 G-7奨学財団 研究開発助成事業
田所友美, 谷口英樹
Authorship：Principal investigator
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回転求心培養法による多階層血管構造を有するヒト臓器の創出
2021.04 - 2022.03
一般財団法人 G-7奨学財団 研究開発助成事業
田所友美, 谷口英樹
Authorship：Principal investigator
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回転求心培養法による多階層血管構造を有するヒト臓器の創出
2020.04 - 2021.03
一般財団法人 G-7奨学財団 研究開発助成事業
田所友美, 谷口英樹
Authorship：Principal investigator
Past of Cooperative Research 【 display / non-display 】
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肝芽保存法の開発
2023.04 - 2024.03
日産化学株式会社 Cooperative Research within Japan
田所友美, 谷口英樹
Authorship：Principal investigator
Presentations 【 display / non-display 】
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細胞遊走法の最適化：細胞の蛍光ラベル法選択と遊走因子の濃度勾配が成功の鍵
田所 友美、加藤 幹茂子、小林 達哉、谷口 英樹
第102回日本生理学会大会・第130回日本解剖学会・第98回日本薬理学会合同会（APPW2025） 2025.03
Event date： 2025.03
Language：English Presentation type：Poster presentation
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微小重力がもたらすヒト臓器創出の新展開：宇宙実験の最新成果 Invited
田所 友美
第47回日本分子生物学会年会 2024.11
Event date： 2024.11
Language：English Presentation type：Symposium, workshop panel (public)
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ヒトiPS 細胞由来肝臓オルガノイド移植による肝硬変治療法の開発―免疫制御を介した新たな再生医療の実現― Invited
田所 友美
第45回Science café 2024.11
Event date： 2024.11
Language：Japanese Presentation type：Public lecture, seminar, tutorial, course, or other speech
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ヒトiPS細胞由来肝臓オルガノイド保存技術の開発
田所 友美, 阿武 志保, 畑中 大輔, 加藤 幹茂子, 林 寿人, 岡本 理志, 小林 正樹, 谷口 英樹
第22回 日本再生医療学会総会 2023.03
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シングルセル解析の実践例：血管階層性構築過程の解析 Invited
田所 友美, 田中 啓介
NGRCセミナー2022 第５回 2023.02
Event date： 2023.02
Language：Japanese Presentation type：Public lecture, seminar, tutorial, course, or other speech
Teaching Experience 【 display / non-display 】
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Stem Cell Biology
2021.06 Institution：Yokohama City University, Graduate School of Medicine, Graduate
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Developmental Biology
2019.06 - 2024.05 Institution：Yokohama City University, Graduate School of Medicine, Graduate
Social Activities 【 display / non-display 】
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シングルセル解析の実践例：血管階層性構築過程の解析
Role(s)： Lecturer
NGRCセミナー2022 第５回 2023.02
Type：Seminar, workshop
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ヒト臓器を宇宙空間で創る！ 〜研究者たちの挑戦〜
Role(s)： Lecturer
Space Medicine Japan Youth Community Space Medicine Japan Youth Community（SMJYC） マンスリーセミナー 2022.08
Type：Seminar, workshop
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幹細胞による気道上皮の維持と再生
Role(s)： Lecturer
第55回日本呼吸器学会サテライトミーティング 呼吸器基礎研究を加速するための若手研究会議 2015.04
Type：Seminar, workshop
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Report on the XVIII International Symposium on Glycoconjugates
Role(s)： Report author
2005.01
Type：Promotional material
Media Coverage 【 display / non-display 】
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iPS細胞由来のオルガノイド移植で肝硬変治療 ミニ肝臓で動物実験成功、臨床試験目指す Newspaper, magazine
産経新聞 2024.08
Author：Other
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肝疾患：オルガノイドを用いた新たな治療法のアプローチが試験される TV or radio program
Deutschlandfunk Forschung aktuell 2024.07
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横浜市立大、ヒトiPS細胞由来の肝臓オルガノイド移植による革新的な肝線維化治療法の開発ー肝硬変に対する免疫制御を介した新規治療法ー Internet
日経バイオテク 2024.07
Author：Other