2024/11/09 更新

写真a

オオツカ タカヨシ
大塚 尭慶
OTSUKA Takayoshi
所属
脳研究所 生命科学リソース研究センター 助教
職名
助教
外部リンク

学位

  • 博士(理学) ( 2016年3月   東京大学 )

研究キーワード

  • 炎症

  • 老化

  • 幹細胞

  • ミトコンドリア

  • 再生

  • 細胞老化

研究分野

  • ライフサイエンス / 発生生物学

経歴(researchmap)

  • 新潟大学   脳研究所附属生命科学リソース研究センター   助教

    2022年7月

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    国名:日本国

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  • UConn Health Center   Connecticut Convergence Institute for Translation in Regenerative Engineering   Post doctoral fellow

    2018年1月 - 2022年6月

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  • University of California, Irvine   Department of Developmental and Cell Biology   Post doctoral fellow

    2016年4月 - 2017年12月

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経歴

  • 新潟大学   脳研究所 生命科学リソース研究センター   助教

    2022年7月 - 現在

学歴

  • 東京大学   理学系研究科   生物科学専攻(博士課程)

    2013年4月 - 2016年3月

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  • 東京大学   理学系研究科   生物科学専攻(修士課程)

    2011年4月 - 2013年3月

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  • 東京大学   理学部   生物学科動物学コース

    2007年4月 - 2011年3月

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論文

  • Development of porcine skeletal muscle extracellular matrix–derived hydrogels with improved properties and low immunogenicity 査読

    Mohammed A. Barajaa, Takayoshi Otsuka, Debolina Ghosh, Ho-Man Kan, Cato T. Laurencin

    Proceedings of the National Academy of Sciences   2024年5月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1073/pnas.2322822121

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  • Extracellular disposal of nuclear waste by APP: a protective mechanism impaired in Alzheimer’s disease

    Godfried Dougnon, Takayoshi Otsuka, Yuka Nakamura, Akiko Sakai, Tomoyuki Yamanaka, Noriko Matsui, Asa Nakahara, Ai Ito, Atsushi Hatano, Masaki Matsumoto, Hironaka Igarashi, Akiyoshi Kakita, Masaki Ueno, Hideaki Matsui

    bioRxiv   2024年2月

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    出版者・発行元:Cold Spring Harbor Laboratory  

    Abstract

    Although the amyloid beta (Aβ) hypothesis<sup>1</sup>has long been central to Alzheimer’s disease (AD) research, effective therapeutic strategies remain elusive<sup>2,3</sup>. Here we re-evaluate the functions of amyloid precursor protein (APP) and reveal its critical function in protecting against nuclear impairment-induced cell death and inflammation<sup>4,5</sup>. Overexpression of APP mitigated etoposide or lamin A knockdown-induced nuclear damage, while APP removal or mutations exacerbated these effects. Interestingly, neurons differentiated from induced pluripotent stem cells (iPSCs) exhibited similar patterns, and notably, familial AD-associated mutant APP failed to confer protection against nuclear impairment. We identify APP’s interaction with a cytoplasmic structure of nuclear origin, termed “nuclear waste”, and propose its role in extracellular waste disposal. Intriguingly, cells lacking APP showed impaired nuclear waste clearance, leading to abnormal cytoplasmic accumulation of the nuclear waste. Similarly, neuron-specific APP overexpression using adeno-associated virus (AAV) in mice reduced neuronal death and inflammation caused by nuclear damage. Conversely, shRNA-mediated APP exacerbated these effects, and mutant APP associated with familial AD lacked protective effects. Moreover, postmortem analysis of AD brains revealed accumulation of abnormal nuclear waste in the neurocytoplasm, irregular nuclear morphology, and reduced APP levels per neuron. Our data underscore APP’s crucial role in disposing of nuclear waste, maintaining cellular homeostasis, and suggest its dysregulation as a potential contributor to AD pathogenesis. Restoring APP waste clearance in AD could be a promising target for disease-modifying therapies.

    DOI: 10.1101/2024.02.10.579739

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  • Fibroblast growth factor 8b (FGF-8b) enhances myogenesis and inhibits adipogenesis in rotator cuff muscle cell populations in vitro 査読

    Takayoshi Otsuka, Ho-Man Kan, Paulos Y. Mengsteab, Breajah Tyson, Cato T. Laurencin

    Proceedings of the National Academy of Sciences   2024年1月

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    担当区分:筆頭著者   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1073/pnas.2314585121

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  • Amnion-Based Biomaterials for Musculoskeletal Regenerative Engineering 査読

    Maumita Bhattacharjee, Takayoshi Otsuka, Godwin K. Dzidotor, Lakshmi S. Nair, Cato T. Laurencin

    Regenerative Engineering and Translational Medicine   2023年11月

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    担当区分:筆頭著者   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s40883-023-00321-1

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  • Efficacy of a Novel Electroconductive Matrix To Treat Muscle Atrophy and Fat Accumulation in Chronic Massive Rotator Cuff Tears of the Shoulder 査読

    Nikoo Saveh Shemshaki, Ho-Man Kan, Mohammed A. Barajaa, Amir Lebaschi, Takayoshi Otsuka, Neha Mishra, Lakshmi S. Nair, Cato T. Laurencin

    ACS Biomaterials Science & Engineering   2023年10月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1021/acsbiomaterials.3c00585

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  • Classes of Stem Cells: From Biology to Engineering 査読

    Shiv Shah, Debolina Ghosh, Takayoshi Otsuka, Cato T. Laurencin

    Regenerative Engineering and Translational Medicine   10 ( 3 )   309 - 322   2023年9月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    DOI: 10.1007/s40883-023-00317-x

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    その他リンク: https://link.springer.com/article/10.1007/s40883-023-00317-x/fulltext.html

  • Fish Models for Exploring Mitochondrial Dysfunction Affecting Neurodegenerative Disorders 査読

    Takayoshi Otsuka, Hideaki Matsui

    International Journal of Molecular Sciences   24 ( 8 )   7079 - 7079   2023年4月

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    担当区分:筆頭著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    Neurodegenerative disorders are characterized by the progressive loss of neuronal structure or function, resulting in memory loss and movement disorders. Although the detailed pathogenic mechanism has not been elucidated, it is thought to be related to the loss of mitochondrial function in the process of aging. Animal models that mimic the pathology of a disease are essential for understanding human diseases. In recent years, small fish have become ideal vertebrate models for human disease due to their high genetic and histological homology to humans, ease of in vivo imaging, and ease of genetic manipulation. In this review, we first outline the impact of mitochondrial dysfunction on the progression of neurodegenerative diseases. Then, we highlight the advantages of small fish as model organisms, and present examples of previous studies regarding mitochondria-related neuronal disorders. Lastly, we discuss the applicability of the turquoise killifish, a unique model for aging research, as a model for neurodegenerative diseases. Small fish models are expected to advance our understanding of the mitochondrial function in vivo, the pathogenesis of neurodegenerative diseases, and be important tools for developing therapies to treat diseases.

    DOI: 10.3390/ijms24087079

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  • Electroconductivity, a regenerative engineering approach to reverse rotator cuff muscle degeneration 査読

    Nikoo Saveh-Shemshaki, Mohammed A Barajaa, Takayoshi Otsuka, Elnaz S Mirdamadi, Lakshmi S Nair, Cato T Laurencin

    Regenerative Biomaterials   2023年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press ({OUP})  

    <jats:title>Abstract</jats:title>
    <jats:p>Muscle degeneration is one the main factors that lead to the high rate of retear after a successful repair of rotator cuff tears. The current surgical practices have failed to treat patients with chronic massive rotator cuff tears. Therefore, regenerative engineering approaches are being studied to address the challenges. Recent studies showed the promising outcomes of electroactive materials on the regeneration of electrically excitable tissues such as skeletal muscle. Here, we review the most important biological mechanism of rotator cuff muscle degeneration. Further, the review covers the recent studies on electroactive materials for muscle regeneration including rotator cuff muscle. Finally, we will discuss the future direction toward the application of electroactive materials for the augmentation of rotator cuff tears.</jats:p>

    DOI: 10.1093/rb/rbad099

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  • Overexpression of NDST1 Attenuates Fibrotic Response in Murine Adipose-Derived Stem Cells 査読

    Takayoshi Otsuka, Ho-Man Kan, Timothy D. Mason, Lakshmi S. Nair, Cato T. Laurencin

    Stem Cells and Development   31 ( 23-24 )   787 - 798   2022年12月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Mary Ann Liebert Inc  

    DOI: 10.1089/scd.2022.0053

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    その他リンク: https://www.liebertpub.com/doi/pdf/10.1089/scd.2022.0053

  • Muscle degeneration in chronic massive rotator cuff tears of the shoulder: Addressing the real problem using a graphene matrix 査読

    Nikoo Saveh Shemshaki, Ho-Man Kan, Mohammed Barajaa, Takayoshi Otsuka, Amir Lebaschi, Neha Mishra, Lakshmi S. Nair, Cato T. Laurencin

    Proceedings of the National Academy of Sciences   2022年8月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1073/pnas.2208106119

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  • Injectable amnion hydrogel-mediated delivery of adipose-derived stem cells for osteoarthritis treatment 査読

    Maumita Bhattacharjee, Jorge L. Escobar Ivirico, Ho-Man Kan, Shiv Shah, Takayoshi Otsuka, Rosalie Bordett, Mohammed Barajaa, Naveen Nagiah, Rishikesh Pandey, Lakshmi S. Nair, Cato T. Laurencin

    Proceedings of the National Academy of Sciences   119 ( 4 )   2022年1月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Proceedings of the National Academy of Sciences  

    DOI: 10.1073/pnas.2120968119

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  • Regenerative Engineering Approaches to Scar-Free Skin Regeneration 査読

    Takayoshi Otsuka, Ho-Man Kan, Cato T. Laurencin

    Regenerative Engineering and Translational Medicine   8 ( 2 )   225 - 247   2021年9月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media {LLC}  

    DOI: 10.1007/s40883-021-00229-8

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    その他リンク: https://link.springer.com/article/10.1007/s40883-021-00229-8/fulltext.html

  • Control of mesenchymal cell fate via application of FGF-8b in vitro 査読

    Takayoshi Otsuka, Paulos Y. Mengsteab, Cato T. Laurencin

    Stem Cell Research   51   102155 - 102155   2021年1月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier {BV}  

    DOI: 10.1016/j.scr.2021.102155

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  • Minimally Invasive Cellular Therapies for Osteoarthritis Treatment 査読

    Shiv Shah, Takayoshi Otsuka, Maumita Bhattacharjee, Cato T. Laurencin

    Regenerative Engineering and Translational Medicine   7 ( 1 )   76 - 90   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media {LLC}  

    DOI: 10.1007/s40883-020-00184-w

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    その他リンク: http://link.springer.com/article/10.1007/s40883-020-00184-w/fulltext.html

  • Mechanically superior matrices promote osteointegration and regeneration of anterior cruciate ligament tissue in rabbits 査読

    Mengsteab, P.Y., Otsuka, T., McClinton, A., Shemshaki, N.S., Shah, S., Kan, H.-M., Obopilwe, E., Vella, A.T., Nair, L.S., Laurencin, C.T.

    Proceedings of the National Academy of Sciences of the United States of America   117 ( 46 )   202012347 - 202012347   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Proceedings of the National Academy of Sciences  

    The gold standard treatment for anterior cruciate ligament (ACL) reconstruction is the use of tendon autografts and allografts. Limiting factors for this treatment include donor site morbidity, potential disease transmission, and variable graft quality. To address these limitations, we previously developed an off-the-shelf alternative, a poly(<sc>l</sc>-lactic) acid (PLLA) bioengineered ACL matrix, and demonstrated its feasibility to regenerate ACL tissue. This study aims to 1) accelerate the rate of regeneration using the bioengineered ACL matrix by supplementation with bone marrow aspirate concentrate (BMAC) and growth factors (BMP-2, FGF-2, and FGF-8) and 2) increase matrix strength retention. Histological evaluation showed robust tissue regeneration in all groups. The presence of cuboidal cells reminiscent of ACL fibroblasts and chondrocytes surrounded by an extracellular matrix rich in anionic macromolecules was up-regulated in the BMAC group. This was not observed in previous studies and is indicative of enhanced regeneration. Additionally, intraarticular treatment with FGF-2 and FGF-8 was found to suppress joint inflammation. To increase matrix strength retention, we incorporated nondegradable fibers, polyethylene terephthalate (PET), into the PLLA bioengineered ACL matrix to fabricate a “tiger graft.” The tiger graft demonstrated the greatest peak loads among the experimental groups and the highest to date in a rabbit model. Moreover, the tiger graft showed superior osteointegration, making it an ideal bioengineered ACL matrix. The results of this study illustrate the beneficial effect bioactive factors and PET incorporation have on ACL regeneration and signal a promising step toward the clinical translation of a functional bioengineered ACL matrix.

    DOI: 10.1073/pnas.2012347117

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    その他リンク: https://syndication.highwire.org/content/doi/10.1073/pnas.2012347117

  • Preparation and characterization of amnion hydrogel and its synergistic effect with adipose derived stem cells towards IL1β activated chondrocytes 査読

    Maumita Bhattacharjee, Jorge L. Escobar Ivirico, Ho-Man Kan, Rosalie Bordett, Rishikesh P, ey, Takayoshi Otsuka, Lakshmi S. Nair, Cato T. Laurencin

    Scientific Reports   10 ( 1 )   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media {LLC}  

    <title>Abstract</title>
    Inflammation leads to chondrocyte senescence and cartilage degeneration, resulting in osteoarthritis (OA). Adipose‐derived stem cells (ADSCs) exert paracrine effects protecting chondrocytes from degenerative changes. However, the lack of optimum delivery systems for ADSCs limits its use in the clinic. The use of extracellular matrix based injectable hydrogels has gained increased attention due to their unique properties. In the present study, we developed hydrogels from amnion tissue as a delivery system for ADSCs. We investigated the potential of amnion hydrogel to maintain ADSC functions, the synergistic effect of AM with ADSC in preventing the catabolic responses of inflammation in stimulated chondrocytes. We also investigated the role of Wnt/β-catenin signaling pathway in IL-1β induced inflammation in chondrocytes and the ability of AM-ADSC to inhibit Wnt/β-catenin signaling. Our results showed that AM hydrogels supported cell viability, proliferation, and stemness. ADSCs, AM hydrogels and AM-ADSCs inhibited the catabolic responses of IL-1β and inhibited the Wnt/β-catenin signaling pathway, indicating possible involvement of Wnt/β-catenin signaling pathways in IL-1β induced inflammation. The results also showed that the synergistic effect of AM-ADSCs was more pronounced in preventing catabolic responses in activated chondrocytes. In conclusion, we showed that AM hydrogels can be used as a potential carrier for ADSCs, and can be developed as a potential therapeutic agent for treating OA.

    DOI: 10.1038/s41598-020-75921-w

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    その他リンク: http://www.nature.com/articles/s41598-020-75921-w

  • Identification of Heparan-Sulfate Rich Cells in the Loose Connective Tissues of the Axolotl (Ambystoma mexicanum) with the Potential to Mediate Growth Factor Signaling during Regeneration 査読

    T. Otsuka, A. Q. Phan, C. T. Laurencin, J. D. Esko, S. V. Bryant, D. M. Gardiner

    Regenerative Engineering and Translational Medicine   6 ( 1 )   7 - 17   2020年1月

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    担当区分:筆頭著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    DOI: 10.1007/s40883-019-00140-3

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    その他リンク: http://link.springer.com/article/10.1007/s40883-019-00140-3/fulltext.html

  • Evaluation of a bioengineered ACL matrix’s osteointegration with BMP-2 supplementation 査読

    Paulos Y. Mengsteab, Patrick Conroy, Mary Badon, Takayoshi Otsuka, Ho-Man Kan, Anthony T. Vella, Lakshmi S. Nair, Cato T. Laurencin

    PLOS ONE   15 ( 1 )   e0227181 - e0227181   2020年1月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Public Library of Science (PLoS)  

    DOI: 10.1371/journal.pone.0227181

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  • The Axolotl Limb Regeneration Model as a Discovery Tool for Engineering the Stem Cell Niche 査読

    Negar Seyedhassantehrani, Takayoshi Otsuka, Shambhavi Singh, David M. Gardiner

    Current Stem Cell Reports   3 ( 3 )   156 - 163   2017年7月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    DOI: 10.1007/s40778-017-0085-5

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    その他リンク: http://link.springer.com/content/pdf/10.1007/s40778-017-0085-5.pdf

  • Targeted Ablation of Pancreatic β Cells in Medaka 査読

    Otsuka Takayoshi, Takeda Hiroyuki

    Zoological science   34 ( 3 )   179 - 184   2017年6月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Zoological Society of Japan  

    DOI: 10.2108/zs170004

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    その他リンク: http://www.bioone.org/doi/pdf/10.2108/zs170004

  • Development of the pancreas in medaka, Oryzias latipes, from embryo to adult 査読

    Otsuka, T., Tsukahara, T., Takeda, H.

    Development Growth and Differentiation   57 ( 8 )   557 - 569   2015年10月

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    担当区分:筆頭著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1111/dgd.12237

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  • Large hypomethylated domains serve as strong repressive machinery for key developmental genes in vertebrates 査読 国際誌

    Ryohei Nakamura, Tatsuya Tsukahara, Wei Qu, Kazuki Ichikawa, Takayoshi Otsuka, Katsumi Ogoshi, Taro L. Saito, Kouji Matsushima, Sumio Sugano, Shinichi Hashimoto, Yutaka Suzuki, Shinichi Morishita, Hiroyuki Takeda

    Development   141 ( 13 )   2568 - 2580   2014年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:The Company of Biologists  

    DNA methylation is a fundamental epigenetic modification in vertebrate genomes and a small fraction of genomic regions is hypomethylated. Previous studies have implicated hypomethylated regions in gene regulation, but their functions in vertebrate development remain elusive. To address this issue, we generated epigenomic profiles that include base-resolution DNA methylomes and histone modification maps from both pluripotent cells and mature organs of medaka fish and compared the profiles with those of human ES cells. We found that a subset of hypomethylated domains harbor H3K27me3 (K27HMDs) and their size positively correlates with the accumulation of H3K27me3. Large K27HMDs are conserved between medaka and human pluripotent cells and predominantly contain promoters of developmental transcription factor genes. These key genes were found to be under strong transcriptional repression, when compared with other developmental genes with smaller K27HMDs. Furthermore, human-specific K27HMDs show an enrichment of neuronal activity-related genes, which suggests a distinct regulation of these genes in medaka and human. In mature organs, some of the large HMDs become shortened by elevated DNA methylation and associate with sustained gene expression. This study highlights the significance of domain size in epigenetic gene regulation. We propose that large K27HMDs play a crucial role in pluripotent cells by strictly repressing key developmental genes, whereas their shortening consolidates long-term gene expression in adult differentiated cells.

    DOI: 10.1242/dev.108548

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▶ 全件表示

受賞

  • 2024年度 武田科学振興財団 医学系研究助成(精神・神経・脳領域)

    2024年11月   公益財団法人武田科学振興財団  

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  • 第23回日本再生医療学会総会 優秀演題賞

    2024年3月   一般社団法人日本再生医療学会  

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  • 令和5年度 塚田医学奨学助成金

    2023年4月   塚田医学奨学基金  

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共同研究・競争的資金等の研究

  • 老化の何が再生を阻害するのか?老化モデル生物アフリカメダカを用いた解析

    研究課題/領域番号:23K14192

    2023年4月 - 2026年3月

    制度名:科学研究費助成事業 若手研究

    研究種目:若手研究

    提供機関:日本学術振興会

    大塚 尭慶

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

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