Regularion of axial stem cells producing various types of somatic cells

• Project/Area Number: 17H03607
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Genome biology
• Research Institution: The University of Tokushima
• Principal Investigator: TAKEMOTO Tatsuya 徳島大学, 先端酵素学研究所, 教授 (30443899)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000); Fiscal Year 2020: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2017: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: 原腸陥入 / 細胞分化 / 転写制御 / 遺伝子発現制御

Outline of Final Research Achievements

We studied the mechanism how various types of differentiated cells are produced from the axial stem cells along the head-tail axis during embryogenesis. We especially focused on the extracellular environment, which acts the gene regulatory network of the axial stem cells (gene expression status and epigenomic status), and elucidated that the nephric mesenchyme (a part of future kidney) is derived from the axial stem cells.

Academic Significance and Societal Importance of the Research Achievements

脊椎動物の初期胚は多能性幹細胞から構成されるが、原腸陥入によって多種多様な体細胞系列が生み出される。こういった、体細胞系列がどういった仕組みで生み出されるかは不明であった。私たちが行なっている一連の研究では、こういった体細胞系列を産み出される仕組みについて、遺伝子制御の観点から明らかにしてきた。胚発生における細胞分化の仕組みを正確に理解することは、理学的な観点のみならず、幹細胞を出発点とした再生医療研究からも重要である。

Research Products

• [Journal Article] PD-1 agonism by anti-CD80 inhibits T cell activation and alleviates autoimmunity (2022)
  • Author(s): Sugiura Daisuke、Okazaki Il-mi、Maeda Takeo K.、Maruhashi Takumi、Shimizu Kenji、Arakaki Rieko、Takemoto Tatsuya、Ishimaru Naozumi、Okazaki Taku
  • Journal Title: Nature Immunology Volume: 23 Issue: 3 Pages: 399-410
  • DOI: 10.1038/s41590-021-01125-7
  • Peer Reviewed / Open Access
• [Journal Article] PD-1 preferentially inhibits the activation of low-affinity T cells (2021)
  • Author(s): Shimizu Kenji、Sugiura Daisuke、Okazaki Il-mi、Maruhashi Takumi、Takemoto Tatsuya、Okazaki Taku
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 118 Issue: 35
  • DOI: 10.1073/pnas.2107141118
  • Peer Reviewed / Open Access
• [Journal Article] The nephric mesenchyme lineage of intermediate mesoderm is derived from Tbx6-expressing derivatives of neuro-mesodermal progenitors via BMP-dependent Osr1 function (2021)
  • Author(s): Hayashi Shinichi、Suzuki Hitomi、Takemoto Tatsuya
  • Journal Title: Developmental Biology Volume: 478 Pages: 155-162
  • DOI: 10.1016/j.ydbio.2021.07.006
  • Peer Reviewed
• [Journal Article] Sox2 gene regulation via the D1 enhancer in embryonic neural tube and neural crest by the combined action of SOX2 and ZIC2 (2020)
  • Author(s): Iida Hideaki、Furukawa Yoko、Teramoto Machiko、Suzuki Hitomi、Takemoto Tatsuya、Uchikawa Masanori、Kondoh Hisato
  • Journal Title: Genes to Cells Volume: In press Issue: 4 Pages: 242-256
  • DOI: 10.1111/gtc.12753
  • Peer Reviewed / Open Access
• [Journal Article] The absence of SOX2 in the anterior foregut alters the esophagus into trachea and bronchi in both epithelial and mesenchymal components (2020)
  • Author(s): Teramoto Machiko、Sugawara Ryo、Minegishi Katsura、Uchikawa Masanori、Takemoto Tatsuya、Kuroiwa Atsushi、Ishii Yasuo、Kondoh Hisato
  • Journal Title: Biology Open Volume: 9 Pages: 048728-048728
  • DOI: 10.1242/bio.048728
  • NAID: 120006859990
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Restriction of PD-1 function by cis-PD-L1/CD80 interactions is required for optimal T cell responses (2019)
  • Author(s): Sugiura Daisuke、Maruhashi Takumi、Okazaki Il-mi、Shimizu Kenji、Maeda Takeo K.、Takemoto Tatsuya、Okazaki Taku
  • Journal Title: Science Volume: 364 Issue: 6440 Pages: 558-566
  • DOI: 10.1126/science.aav7062
  • Peer Reviewed
• [Journal Article] Hoxa13 regulates expression of common Hox target genes involved in cartilage development to coordinate the expansion of the autopodal anlage (2019)
  • Author(s): Yamamoto Shiori、Uchida Yuji、Ohtani Tomomi、Nozaki Erina、Yin Chunyang、Gotoh Yoshihiro、Yakushiji‐Kaminatsui Nayuta、Higashiyama Tetsuya、Suzuki Takamasa、Takemoto Tatsuya、Shiraishi Yo‐ichi、Kuroiwa Atsushi
  • Journal Title: Development, Growth & Differentiation Volume: 61 Issue: 3 Pages: 228-251
  • DOI: 10.1111/dgd.12601
  • NAID: 120006941124
  • Peer Reviewed / Open Access
• [Journal Article] Zygote Electroporation for CRISPR/Cas9 Delivery to Generate Genetically Modified Mice (2019)
  • Author(s): Takemoto Tatsuya
  • Journal Title: Methods in Molecular Biology Volume: 2050 Pages: 121-126
  • DOI: 10.1007/978-1-4939-9740-4_13
  • ISBN: 9781493997398, 9781493997404
  • Peer Reviewed
• [Journal Article] Histone H3.3 sub-variant H3mm7 is required for normal skeletal muscle regeneration (2018)
  • Author(s): Harada Akihito、Maehara Kazumitsu、Ono Yusuke、Taguchi Hiroyuki、Yoshioka Kiyoshi、Kitajima Yasuo、Xie Yan、Sato Yuko、Iwasaki Takeshi、Nogami Jumpei、Okada Seiji、Komatsu Tetsuro、Semba Yuichiro、Takemoto Tatsuya、Kimura Hiroshi、Kurumizaka Hitoshi、Ohkawa Yasuyuki
  • Journal Title: Nature Communications Volume: 9 Issue: 1 Pages: 1400-1400
  • DOI: 10.1038/s41467-018-03845-1
  • NAID: 120006949474
  • Peer Reviewed / Open Access
• [Journal Article] Generation of a TP53-modified porcine cancer model by CRISPR/Cas9-mediated gene modification in porcine zygotes via electroporation (2018)
  • Author(s): Tanihara Fuminori、Hirata Maki、Nguyen Nhien Thi、Le Quynh Anh、Hirano Takayuki、Takemoto Tatsuya、Nakai Michiko、Fuchimoto Dai-ichiro、Otoi Takeshige
  • Journal Title: PLOS ONE Volume: 13 Issue: 10 Pages: e0206360-e0206360
  • DOI: 10.1371/journal.pone.0206360
  • NAID: 120006548638
  • Peer Reviewed / Open Access
• [Journal Article] Generation of PDX-1 mutant porcine blastocysts by introducing CRISPR/Cas9-system into porcine zygotes via electroporation (2018)
  • Author(s): Tanihara Fuminori、Hirata Maki、Nguyen Nhien T.、Le Quynh A.、Hirano Takayuki、Takemoto Tatsuya、Nakai Michiko、Fuchimoto Dai-ichiro、Otoi Takeshige
  • Journal Title: Animal Science Journal Volume: 90 Issue: 1 Pages: 55-61
  • DOI: 10.1111/asj.13129
  • Peer Reviewed / Open Access
• [Presentation] 体軸幹細胞の制御におけるGreb1の役割 (2019)
  • Author(s): Takami N, Hayashi S, Takemoto T.
  • Organizer: 52nd Annual Meeting of the Japanese Society of Developmental Biologists.
• [Presentation] 中胚葉細胞の移動は中胚葉誘導因子であるcTbx6Lに依存しない (2019)
  • Author(s): Shimokita E, Suzuki H, Tsuruo Y, Takemoto T.
  • Organizer: 52nd Annual Meeting of the Japanese Society of Developmental Biologists.
• [Presentation] マウス体軸形成において体軸幹細胞は中間中胚葉を産み出す (2019)
  • Author(s): Hayashi S, Takemoto T.
  • Organizer: 52nd Annual Meeting of the Japanese Society of Developmental Biologists.
• [Presentation] 後肢の位置を決定するGdf11のエンハンサーの同定とトランス因子の重要性 (2019)
  • Author(s): Saito S, Kanazawa U, Hibino N, Takemoto T, Matsuda Y, Kuroiwa A, Suzuki T.
  • Organizer: 52nd Annual Meeting of the Japanese Society of Developmental Biologists.
• [Presentation] 後肢の位置を決定するGdf11のエンハンサーの同定と機能的解析 (2019)
  • Author(s): 5.Saito S, Kanazawa U, Hibino N, Takemoto T, Matsuda Y, Kuroiwa A, Suzuki T.
  • Organizer: 52nd Annual Meeting of the Japanese Society of Developmental Biologists.
• [Remarks] 徳島大学先端酵素学研究所発生生物学分野ホームページ
  • URL: http://www.fujii.tokushima-u.ac.jp/embryology/
• [Remarks] 徳島大学先端酵素学研究所 発生生物学分野
  • URL: http://www.fujii.tokushima-u.ac.jp/embryology/