Mechanisms of maintenance and regeneration of pluripotent stem cells

• Project Area: Principles of pluripotent stem cells underlying plant vitality
• Project/Area Number: 17H06477
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: Umeda Masaaki 奈良先端科学技術大学院大学, 先端科学技術研究科, 教授 (80221810)
• Co-Investigator(Kenkyū-buntansha): 蓑田 亜希子 国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (40721569) ; 坪内 知美 基礎生物学研究所, 幹細胞生物学研究室, 准教授 (70754505)
• Project Period (FY): 2017-06-30 – 2022-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥212,810,000 (Direct Cost: ¥163,700,000、Indirect Cost: ¥49,110,000); Fiscal Year 2021: ¥46,800,000 (Direct Cost: ¥36,000,000、Indirect Cost: ¥10,800,000); Fiscal Year 2020: ¥46,800,000 (Direct Cost: ¥36,000,000、Indirect Cost: ¥10,800,000); Fiscal Year 2019: ¥46,800,000 (Direct Cost: ¥36,000,000、Indirect Cost: ¥10,800,000); Fiscal Year 2018: ¥46,800,000 (Direct Cost: ¥36,000,000、Indirect Cost: ¥10,800,000); Fiscal Year 2017: ¥25,610,000 (Direct Cost: ¥19,700,000、Indirect Cost: ¥5,910,000)
• Keywords: 多能性幹細胞 / DNA損傷 / ゲノム恒常性 / クロマチン / ES細胞 / 幹細胞 / 多能性 / 1細胞解析

Outline of Final Research Achievements

In this study, we aimed to elucidate the molecular mechanisms of stem cell maintenance. First, we identified the mechanism of G2 arrest in response to DNA damage in Arabidopsis roots. We also elucidated the mechanism by which phytohormones regulate genome stability and stem cell regeneration. Furthermore, we revealed that in mammalian ES cells, a number of replication machinery that slowly synthesizes DNA is located on the genome.

Academic Significance and Societal Importance of the Research Achievements

本研究により、DNA損傷に応答した細胞周期停止に新規なシグナル伝達経路が関与することが明らかになった。また、植物ホルモンが、DNA損傷により誘導される幹細胞特異的な細胞死を制御していることが示され、その後の幹細胞再生にもホルモンシグナリングの活性化が関与している可能性が示唆された。さらに、哺乳類ES細胞において、多能性・細胞周期進行・DNA複製の協調的制御の一端が明らかとなり、幹細胞の維持機構の理解につながった。

Research Products

• [Int'l Joint Research] CBM/CRAG(スペイン)
• [Int'l Joint Research] ハンブルク大学(ドイツ)
• [Int'l Joint Research] VIB(ベルギー)
• [Int'l Joint Research] サセックス大学(英国)
• [Int'l Joint Research] CRAG(スペイン)
• [Int'l Joint Research] メリーランド大学(米国)
• [Int'l Joint Research] VIB(ベルギー)
• [Int'l Joint Research] サセックス大学(英国)
• [Int'l Joint Research] CRAG(スペイン)
• [Int'l Joint Research] ハンブルク大学(ドイツ)
• [Int'l Joint Research] サセックス大学(英国)
• [Int'l Joint Research] CRAG(スペイン)
• [Int'l Joint Research] ハンブルク大学(ドイツ)
• [Int'l Joint Research] サセックス大学(英国)
• [Int'l Joint Research] CRAG(スペイン)
• [Int'l Joint Research] ハンブルク大学(ドイツ)
• [Int'l Joint Research] スウェーデン農業大学(スウェーデン)
• [Int'l Joint Research] サセックス大学(英国)
• [Journal Article] Brassinosteroids are required for efficient root tip regeneration in <i>Arabidopsis</i> (2022)
  • Author(s): Takahashi Naoki、Umeda Masaaki
  • Journal Title: Plant Biotechnology Volume: 39 Issue: 1 Pages: 73-78
  • DOI: 10.5511/plantbiotechnology.21.1103a
  • NAID: 130008128861
  • ISSN: 1342-4580, 1347-6114
  • Year and Date: 2022-03-25
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Alterations in hormonal signals spatially coordinate distinct responses to DNA double-strand breaks in Arabidopsis roots (2021)
  • Author(s): Takahashi Naoki、Inagaki Soichi、Nishimura Kohei、Sakakibara Hitoshi、Antoniadi Ioanna、Karady Michal、Ljung Karin、Umeda Masaaki
  • Journal Title: Science Advances Volume: 7 Issue: 25
  • DOI: 10.1126/sciadv.abg0993
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Plant stem cell research is uncovering the secrets of longevity and persistent growth (2021)
  • Author(s): Umeda Masaaki、Ikeuchi Momoko、Ishikawa Masaki、Ito Toshiro、Nishihama Ryuichi、Kyozuka Junko、Torii Keiko U.、Satake Akiko、Goshima Gohta、Sakakibara Hitoshi
  • Journal Title: The Plant Journal Volume: Online ahead of print Issue: 2 Pages: 1-10
  • DOI: 10.1111/tpj.15184
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Regulation of the Plant Cell Cycle in Response to Hormones and the Environment (2021)
  • Author(s): Shimotohno Akie、Aki Shiori S.、Takahashi Naoki、Umeda Masaaki
  • Journal Title: Annual Review of Plant Biology Volume: 72 Issue: 1 Pages: 72-78
  • DOI: 10.1146/annurev-arplant-080720-103739
  • Peer Reviewed
• [Journal Article] Genome Maintenance Mechanisms at the Chromatin Level (2021)
  • Author(s): Takatsuka Hirotomo、Shibata Atsushi、Umeda Masaaki
  • Journal Title: International Journal of Molecular Sciences Volume: 22 Issue: 19 Pages: 10384-10384
  • DOI: 10.3390/ijms221910384
  • Peer Reviewed / Open Access
• [Journal Article] TheArabidopsisNRT1/PTR FAMILY protein NPF7.3/NRT1.5 is an indole-3-butyric acid transporter involved in root gravitropism (2020)
  • Author(s): Watanabe Shunsuke、Takahashi Naoki、Kanno Yuri、Suzuki Hiromi、Aoi Yuki、Takeda-Kamiya Noriko、Toyooka Kiminori、Kasahara Hiroyuki、Hayashi Ken-ichiro、Umeda Masaaki、Seo Mitsunori
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 117 Issue: 49 Pages: 31500-31509
  • DOI: 10.1073/pnas.2013305117
  • Peer Reviewed / Open Access
• [Journal Article] CDKD-dependent activation of CDKA;1 controls microtubule dynamics and cytokinesis during meiosis (2020)
  • Author(s): Sofroni Kostika、Takatsuka Hirotomo、Yang Chao、Dissmeyer Nico、Komaki Shinichiro、Hamamura Yuki、Bottger Lev、Umeda Masaaki、Schnittger Arp
  • Journal Title: Journal of Cell Biology Volume: 219 Issue: 8
  • DOI: 10.1083/jcb.201907016
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] SUPPRESSOR OF GAMMA RESPONSE 1 acts as a regulator coordinating crosstalk between DNA damage response and immune response in Arabidopsis thaliana (2020)
  • Author(s): Yoshiyama Kaoru Okamoto、Aoshima Naoki、Takahashi Naoki、Sakamoto Tomoaki、Hiruma Kei、Saijo Yusuke、Hidema Jun、Umeda Masaaki、Kimura Seisuke
  • Journal Title: Plant Molecular Biology Volume: 103 Issue: 3 Pages: 321-340
  • DOI: 10.1007/s11103-020-00994-0
  • Peer Reviewed
• [Journal Article] A regulatory module controlling stress-induced cell cycle arrest in Arabidopsis (2019)
  • Author(s): Takahashi Naoki、Ogita Nobuo、Takahashi Tomonobu、Taniguchi Shoji、Tanaka Maho、Seki Motoaki、Umeda Masaaki
  • Journal Title: eLife Volume: 8
  • DOI: 10.7554/elife.43944
  • NAID: 120006619181
  • Peer Reviewed / Open Access
• [Journal Article] Cytokinin signaling is essential for organ formation in Marchantia polymorpha (2019)
  • Author(s): Aki Shiori S、Mikami Tatsuya、Naramoto Satoshi、Nishihama Ryuichi、Ishizaki Kimitsune、Kojima Mikiko、Takebayashi Yumiko、Sakakibara Hitoshi、Kyozuka Junko、Kohchi Takayuki、Umeda Masaaki
  • Journal Title: Plant and Cell Physiology Volume: 60 Issue: 8 Pages: 1842-1854
  • DOI: 10.1093/pcp/pcz100
  • NAID: 120006711216
  • Peer Reviewed
• [Journal Article] Cytokinin signaling coordinates development of diverse organs in Marchantia polymorpha (2019)
  • Author(s): Aki Shiori S.、Nishihama Ryuichi、Kohchi Takayuki、Umeda Masaaki
  • Journal Title: Plant Signaling & Behavior Volume: 14 Issue: 11 Pages: 1668232-1668232
  • DOI: 10.1080/15592324.2019.1668232
  • NAID: 120006731887
  • Peer Reviewed
• [Journal Article] Gap 2 phase: making the fundamental decision to divide or not (2019)
  • Author(s): Umeda Masaaki、Aki Shiori S、Takahashi Naoki
  • Journal Title: Current Opinion in Plant Biology Volume: 51 Pages: 1-6
  • DOI: 10.1016/j.pbi.2019.03.001
  • Peer Reviewed
• [Journal Article] Editorial overview: How plants transform signaling cues into changes in gene expression (2019)
  • Author(s): Hwang Ildoo、Umeda Masaaki
  • Journal Title: Current Opinion in Plant Biology Volume: 51 Pages: A1-A3
  • DOI: 10.1016/j.pbi.2019.09.006
  • Int'l Joint Research
• [Journal Article] ABA inhibits root cell elongation through repressing the cytokinin signaling (2019)
  • Author(s): Takatsuka Hirotomo、Umeda Masaaki
  • Journal Title: Plant Signaling & Behavior Volume: 14 Issue: 3 Pages: e1578632-e1578632
  • DOI: 10.1080/15592324.2019.1578632
  • NAID: 120006731888
  • Peer Reviewed
• [Journal Article] Identifying the target genes of SUPPRESSOR OF GAMMA RESPONSE 1, a master transcription factor controlling DNA damage response in Arabidopsis. (2018)
  • Author(s): Ogita N, Okushima Y, Tokizawa M, Yamamoto YY, Tanaka M, Seki M, Makita Y, Matsui M, Okamoto-Yoshiyama K, Sakamoto T, Kurata T, Hiruma K, Saijo Y, Takahashi N, Umeda M.
  • Journal Title: The Plant Journal Volume: - Issue: 3 Pages: 439-453
  • DOI: 10.1111/tpj.13866
  • Peer Reviewed / Open Access
• [Journal Article] Actin reorganization triggers rapid cell elongation in roots (2018)
  • Author(s): Takatsuka Hirotomo、Higaki Takumi、Umeda Masaaki
  • Journal Title: Plant Physiology Volume: 178 Issue: 3 Pages: 1130-1141
  • DOI: 10.1104/pp.18.00557
  • Peer Reviewed
• [Journal Article] Arabidopsis R1R2R3-Myb proteins are essential for inhibiting cell division in response to DNA damage (2017)
  • Author(s): Chen Poyu、Takatsuka Hirotomo、Takahashi Naoki、Kurata Rie、Fukao Yoichiro、Kobayashi Kosuke、Ito Masaki、Umeda Masaaki
  • Journal Title: Nature Communications Volume: 8 Issue: 1 Pages: 635-635
  • DOI: 10.1038/s41467-017-00676-4
  • NAID: 120006354238
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] ブラシノステロイドは根端切除後の幹細胞ニッチの再構築を促進する (2022)
  • Author(s): 高橋直紀、梅田正明
  • Organizer: 第63回日本植物生理学会年会
• [Presentation] Genome maintenance strategies in plant stem cells (2022)
  • Author(s): 梅田正明、安喜史織、高橋直紀
  • Organizer: 第63回日本植物生理学会年会
  • Invited
• [Presentation] オーキシンによるゲノム恒常性維持機構 (2022)
  • Author(s): 安喜史織、梅田正明
  • Organizer: 第63回日本植物生理学会年会
• [Presentation] 植物成長を制御する分子メカニズムの解明 (2021)
  • Author(s): 梅田正明
  • Organizer: 第38回日本植物バイオテクノロジー学会大会
  • Invited
• [Presentation] 細胞間コミュニケーションを介した植物幹細胞の維持機構 (2021)
  • Author(s): 梅田正明、杉山輝樹、紀平望帆
  • Organizer: 第44回日本分子生物学会年会
  • Invited
• [Presentation] DNA損傷に応答したシロイヌナズナの根の幹細胞再生に関する解析 (2021)
  • Author(s): 吹田宗樹、高橋直紀、梅田正明
  • Organizer: 第62回日本植物生理学会年会
• [Presentation] DNA損傷応答におけるインドール酪酸輸送の役割の解明 (2021)
  • Author(s): 高橋直紀、吉國早希、梅田正明
  • Organizer: 第62回日本植物生理学会年会
• [Presentation] オーキシンを介したヘテロクロマチン形成の制御機構 (2021)
  • Author(s): 安喜史織、梅田正明
  • Organizer: 第62回日本植物生理学会年会
• [Presentation] DNA損傷に応答した細胞周期停止の制御機構の解明 (2021)
  • Author(s): 細谷美遥、高橋直紀、梅田正明
  • Organizer: 第62回日本植物生理学会年会
• [Presentation] Role of cell cycle regulation in cell fate determination (2020)
  • Author(s): 杉山輝樹、梅田正明
  • Organizer: 日本植物学会第84回大会
  • Invited
• [Presentation] DNA損傷に応答した根の成長抑制におけるサイトカイニン合成の役割 (2020)
  • Author(s): 高橋直紀、Ioanna Antoniadi、Michal Karady、Karin Ljung、梅田正明
  • Organizer: 日本植物学会第84回大会
• [Presentation] Regulation of DNA replication in mammalian pluripotent stem cells (2020)
  • Author(s): Yasunao Kamikawa、Akino Matsumoto、Tomomi Tsubouchi
  • Organizer: JSDB Online Meeting
• [Presentation] DNA損傷に応答したANAC044/085によるG2期停止機構 (2020)
  • Author(s): 森夏実、高橋直紀、梅田正明
  • Organizer: 第61回日本植物生理学会年会
• [Presentation] DNA損傷応答を制御するヒストン脱アセチル化酵素の機能解析 (2020)
  • Author(s): 辻幸、安喜史織、梅田正明
  • Organizer: 第61回日本植物生理学会年会
• [Presentation] Regulatory mechanism of stem cell maintenance in Arabidopsis roots (2020)
  • Author(s): 髙橋直紀、梅田正明
  • Organizer: 第61回日本植物生理学会年会
  • Invited
• [Presentation] クロマチン制御によるゲノム恒常性維持機構 (2020)
  • Author(s): 安喜史織、梅田正明
  • Organizer: 第61回日本植物生理学会年会
  • Invited
• [Presentation] Genome maintenance strategies in stem cells (2019)
  • Author(s): 梅田正明、安喜史織、高橋直紀
  • Organizer: International Symposium: Principles of pluripotent stem cells underlying plant vitality
  • Int'l Joint Research / Invited
• [Presentation] ストレスに応答した細胞分裂制御 (2019)
  • Author(s): 髙橋直紀、梅田正明
  • Organizer: 日本植物学会第83回大会
  • Invited
• [Presentation] The developmental role of cytokinins in Marchantia polymorpha (2019)
  • Author(s): Shiori S. Aki, Tatsuya Mikami, Satoshi Naramoto, Ryuichi Nishihama, Kimitsune Ishizaki, Mikiko Kojima, Yumiko Takebayashi, Hitoshi Sakakibara, Junko Kyozuka, Takayuki Kohchi, Masaaki Umeda
  • Organizer: Marchantia Workshop 2019
  • Int'l Joint Research
• [Presentation] A regulatory module controlling cell cycle arrest in response to multiple stresses (2019)
  • Author(s): 梅田正明、髙橋直紀
  • Organizer: Plant Cell & Developmental Biology: Cold Spring Harbor Conferences Asia
  • Int'l Joint Research / Invited
• [Presentation] Genotoxic stress inhibits root growth by enhancing cytokinin biosynthesis above the meristem (2019)
  • Author(s): 髙橋直紀、梅田正明
  • Organizer: Plant Cell & Developmental Biology: Cold Spring Harbor Conferences Asia
  • Int'l Joint Research
• [Presentation] Gene regulatory networks in root nodule symbiosis (2019)
  • Author(s): Kai Battenberg, Tsuneo Hakoyama, Atsuko Hirota, Akihiro Yamazaki, Shiori Aki, Masaaki Umeda, Thomas Kelly, Nicola Hetherington, Aki Minoda
  • Organizer: 第60回日本植物生理学会
  • Invited
• [Presentation] Genome maintenance strategies in stem cells (2019)
  • Author(s): 梅田正明
  • Organizer: 第60回日本植物生理学会
  • Invited
• [Presentation] DNA損傷に応答した細胞周期停止を制御する転写因子複合体の同定 (2019)
  • Author(s): 高橋知伸、荻田伸夫、谷口昌司、高橋直紀、梅田正明
  • Organizer: 第60回日本植物生理学会
• [Presentation] ストレスに応答した細胞周期停止の制御機構の解明 (2019)
  • Author(s): 高橋直紀、荻田伸夫、高橋知伸、谷口昌司、梅田正明
  • Organizer: 第60回日本植物生理学会
• [Presentation] DNA damage activates two distinct signaling pathways controlling DNA repair and cell cycle arrest (2018)
  • Author(s): 高橋直紀、荻田伸夫、梅田正明
  • Organizer: Plant Genome Stability and Change 2018
  • Int'l Joint Research
• [Presentation] Control of stem cell division by fine-tuning cyclin-dependent kinase activity (2018)
  • Author(s): 杉山輝樹、高塚大知、梅田正明
  • Organizer: Auxin and Cytokinin in Plant Development
  • Int'l Joint Research
• [Presentation] DNA damage responses in Arabidopsis roots (2018)
  • Author(s): 梅田正明、荻田伸夫、高橋直紀
  • Organizer: 日本遺伝学会第90回大会
  • Invited
• [Presentation] 植物のストレスに応答した細胞周期停止の分子機構 (2018)
  • Author(s): 高橋直紀、荻田伸夫、梅田正明
  • Organizer: 日本遺伝学会第90回大会
• [Presentation] Developing a single-cell bioinformatics analysis pipeline: Application of single-cell RNA-Seq to plant tissues (2018)
  • Author(s): S. Thomas Kelly, Nicola A. Hetherington, Shiori Aki, Haruka Yabukami, Kai Battenberg, Makoto Hayashi, Masaaki Umeda, Akiko Minoda
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] 植物ホルモンによるクロマチン構造変化を介したゲノム恒常性維持機構 (2018)
  • Author(s): 安喜史織、Aida Nazlyn Binti Nazari、高橋直紀、高塚大知、梅田正明
  • Organizer: 第41回日本分子生物学会年会
  • Invited
• [Presentation] 多能性幹細胞におけるDNA複製ストレス応答 (2018)
  • Author(s): 上川泰直、坪内知美
  • Organizer: 日本遺伝学会第90回大会
  • Invited
• [Presentation] Unique regulation of dNTP production in mammalian pluripotent stem cells (2018)
  • Author(s): 上川泰直、坪内知美
  • Organizer: EMBO Workshop on DNA Replication, Chromosome Segregation and Fate Decisions
  • Int'l Joint Research
• [Presentation] 多能性幹細胞におけるDNA複製完了のメカニズム (2018)
  • Author(s): 上川泰直、坪内知美
  • Organizer: 第41回日本分子生物学会年会
  • Invited
• [Presentation] 複製フォーク動態を介した多能性幹細胞におけるゲノム安定性維持機構 (2018)
  • Author(s): 上川泰直、坪内知美
  • Organizer: 第41回日本分子生物学会年会
  • Invited
• [Presentation] ゼニゴケにおけるサイトカイニンレスポンスレギュレーターの機能解析 (2018)
  • Author(s): 安喜史織、三神達也、西浜竜一、小嶋美紀子、竹林裕美子、榊原均、河内孝之、梅田正明
  • Organizer: 第59回日本植物生理学会年会
• [Presentation] CDK阻害因子による幹細胞維持機構の解明 (2018)
  • Author(s): 杉山輝樹、野口博史、高塚大知、梅田正明
  • Organizer: 第59回日本植物生理学会年会
• [Presentation] ANAC044およびANAC085はDNA損傷による細胞周期停止に必要である (2018)
  • Author(s): 高橋直紀、荻田伸夫、高橋知伸、谷口昌司、梅田正明
  • Organizer: 第59回日本植物生理学会年会
• [Presentation] Control of chromatin structure along differentiation trajectories (2018)
  • Author(s): 高塚大知、梅田正明
  • Organizer: 第59回日本植物生理学会年会
  • Invited
• [Presentation] Genome maintenance mechanisms in mammalian pluripotent stem cells (2018)
  • Author(s): 上川泰直、坪内知美
  • Organizer: 第59回日本植物生理学会年会
  • Invited
• [Presentation] Maintenance of genome integrity in root stem cells (2017)
  • Author(s): 梅田正明
  • Organizer: Taiwan-Japan Plant Biology 2017
  • Int'l Joint Research / Invited
• [Presentation] Maintenance of genome integrity in root stem cells (2017)
  • Author(s): 梅田正明
  • Organizer: Plant Cell and Developmental Biology: Approaches to Multiscale Biosystems
  • Int'l Joint Research / Invited
• [Presentation] 植物幹細胞の神秘を探る (2017)
  • Author(s): 梅田正明
  • Organizer: 植物科学シンポジウム2017：植物科学のバイオ農業への展開
  • Invited
• [Presentation] Toward understanding of cytokinin-mediated control of organogenesis (2017)
  • Author(s): 安喜史織、梅田正明
  • Organizer: Marchantia Workshop 2017: Renaissance of Marchantia polymorpha - the genome and beyond
  • Int'l Joint Research / Invited
• [Presentation] 多能性細胞におけるDNA複製とゲノム恒常性 (2017)
  • Author(s): 上川泰直、坪内知美
  • Organizer: 第40回日本分子生物学会年会
• [Remarks] 梅田研ホームページ
  • URL: https://bsw3.naist.jp/umeda/
• [Remarks] 坪内研ホームページ
  • URL: http://www.nibb.ac.jp/stemcell/