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大学院医学系研究科（医学専攻等） 医学専攻 病態制御医学系 分子機能学・代謝機能学講座 |
職務経歴（学外） 【 表示 ／ 非表示 】
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2022年04月-2023年10月
東北大学 大学院医学系研究科 准教授
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2017年04月-2022年03月
東京大学 先端科学技術研究センター 代謝医学分野 准教授
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2012年04月-2017年03月
東京大学 先端科学技術研究センター 代謝医学分野 助教
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2011年04月-2012年03月
東京大学 先端科学技術研究センター 代謝医学分野 特任助教
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2004年06月-2008年01月
秋田大学 医学部 博士研究員
研究分野 【 表示 ／ 非表示 】
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ライフサイエンス / システムゲノム科学 / エピジェネティクス、次世代シーケンス解析
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ライフサイエンス / 分子生物学 / ヒストン修飾、RNA修飾
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ライフサイエンス / 代謝、内分泌学 / 代謝、脂肪細胞
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ライフサイエンス / 細胞生物学
研究等業績 【 表示 ／ 非表示 】
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Hiroki Takahashi, Ryo Ito, Yoshihiro Matsumura, Juro Sakai
BioEssays : news and reviews in molecular, cellular and developmental biology ( BioEssays ) 46 ( 2 ) e2300084 2023年11月 [査読有り]
研究論文（学術雑誌） 国内共著
Organisms must adapt to environmental stresses to ensure their survival and prosperity. Different types of stresses, including thermal, mechanical, and hypoxic stresses, can alter the cellular state that accompanies changes in gene expression but not the cellular identity determined by a chromatin state that remains stable throughout life. Some tissues, such as adipose tissue, demonstrate remarkable plasticity and adaptability in response to environmental cues, enabling reversible cellular identity changes; however, the mechanisms underlying these changes are not well understood. We hypothesized that positive and/or negative "Integrators" sense environmental cues and coordinate the epigenetic and transcriptional pathways required for changes in cellular identity. Adverse environmental factors such as pollution disrupt the coordinated control contributing to disease development. Further research based on this hypothesis will reveal how organisms adapt to fluctuating environmental conditions, such as temperature, extracellular matrix stiffness, oxygen, cytokines, and hormonal cues by changing their cellular identities.
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Hypoxia activates SREBP2 through Golgi disassembly in bone marrow-derived monocytes for enhanced tumor growth.
Ryuichi Nakahara, Sho Aki, Maki Sugaya, Haruka Hirose, Miki Kato, Keisuke Maeda, Daichi M Sakamoto, Yasuhiro Kojima, Miyuki Nishida, Ritsuko Ando, Masashi Muramatsu, Melvin Pan, Rika Tsuchida, Yoshihiro Matsumura, Hideyuki Yanai, Hiroshi Takano, Ryoji Yao, Shinsuke Sando, Masabumi Shibuya, Juro Sakai, Tatsuhiko Kodama, Hiroyasu Kidoya, Teppei Shimamura, Tsuyoshi Osawa
The EMBO journal e114032 2023年10月 [査読有り]
研究論文（学術雑誌） 国内共著
Bone marrow-derived cells (BMDCs) infiltrate hypoxic tumors at a pre-angiogenic state and differentiate into mature macrophages, thereby inducing pro-tumorigenic immunity. A critical factor regulating this differentiation is activation of SREBP2-a well-known transcription factor participating in tumorigenesis progression-through unknown cellular mechanisms. Here, we show that hypoxia-induced Golgi disassembly and Golgi-ER fusion in monocytic myeloid cells result in nuclear translocation and activation of SREBP2 in a SCAP-independent manner. Notably, hypoxia-induced SREBP2 activation was only observed in an immature lineage of bone marrow-derived cells. Single-cell RNA-seq analysis revealed that SREBP2-mediated cholesterol biosynthesis was upregulated in HSCs and monocytes but not in macrophages in the hypoxic bone marrow niche. Moreover, inhibition of cholesterol biosynthesis impaired tumor growth through suppression of pro-tumorigenic immunity and angiogenesis. Thus, our findings indicate that Golgi-ER fusion regulates SREBP2-mediated metabolic alteration in lineage-specific BMDCs under hypoxia for tumor progression.
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Epitranscriptomics in metabolic disease.
Yoshihiro Matsumura, Fan-Yan Wei, Juro Sakai
Nature Metabolism ( Nature Metabolism ) 5 ( 3 ) 370 - 384 2023年03月 [査読有り]
研究論文（学術雑誌） 国内共著
While epigenetic modifications of DNA and histones play main roles in gene transcription regulation, recently discovered post-transcriptional RNA modifications, known as epitranscriptomic modifications, have been found to have a profound impact on gene expression by regulating RNA stability, localization and decoding efficiency. Importantly, genetic variations or environmental perturbations of epitranscriptome modifiers (that is, writers, erasers and readers) are associated with obesity and metabolic diseases, such as type 2 diabetes. The epitranscriptome is closely coupled to epigenetic signalling, adding complexity to our understanding of gene expression in both health and disease. Moreover, the epitranscriptome in the parental generation can affect organismal phenotypes in the next generation. In this Review, we discuss the relationship between epitranscriptomic modifications and metabolic diseases, their relationship with the epigenome and possible therapeutic strategies.
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Glutamine deficiency in solid tumor cells confers resistance to ribosomal RNA synthesis inhibitors
Melvin Pan, Christiane Zorbas, Maki Sugaya, Kensuke Ishiguro, Miki Kato, Miyuki Nishida, Hai-Feng Zhang, Marco M Candeias, Akimitsu Okamoto, Takamasa Ishikawa, Tomoyoshi Soga, Hiroyuki Aburatani, Juro Sakai, Yoshihiro Matsumura, Tsutomu Suzuki, Christopher G Proud, Denis L J Lafontaine, Tsuyoshi Osawa
Nature Communications ( Nature Communications ) 13 ( 1 ) 3706 - 3706 2022年12月 [査読有り]
研究論文（学術雑誌） 国際共著
Ribosome biogenesis is an energetically expensive program that is dictated by nutrient availability. Here we report that nutrient deprivation severely impairs precursor ribosomal RNA (pre-rRNA) processing and leads to the accumulation of unprocessed rRNAs. Upon nutrient restoration, pre-rRNAs stored under starvation are processed into mature rRNAs that are utilized for ribosome biogenesis. Failure to accumulate pre-rRNAs under nutrient stress leads to perturbed ribosome assembly upon nutrient restoration and subsequent apoptosis via uL5/uL18-mediated activation of p53. Restoration of glutamine alone activates p53 by triggering uL5/uL18 translation. Induction of uL5/uL18 protein synthesis by glutamine is dependent on the translation factor eukaryotic elongation factor 2 (eEF2), which is in turn dependent on Raf/MEK/ERK signaling. Depriving cells of glutamine prevents the activation of p53 by rRNA synthesis inhibitors. Our data reveals a mechanism that tumor cells can exploit to suppress p53-mediated apoptosis during fluctuations in environmental nutrient availability.
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Hiroki Takahashi, Ge Yang, Takeshi Yoneshiro, Yohei Abe, Ryo Ito, Chaoran Yang, Junna Nakazono, Mayumi Okamoto-Katsuyama, Aoi Uchida, Makoto Arai, Hitomi Jin, Hyunmi Choi, Myagmar Tumenjargal, Shiyu Xie, Ji Zhang, Hina Sagae, Yanan Zhao, Rei Yamaguchi, Yu Nomura, Yuichi Shimizu, Kaito Yamada, Satoshi Yasuda, Hiroshi Kimura, Toshiya Tanaka, Youichiro Wada, Tatsuhiko Kodama, Hiroyuki Aburatani, Min-Sheng Zhu, Takeshi Inagaki, Timothy F Osborne, Takeshi Kawamura, Yasushi Ishihama, Yoshihiro Matsumura, Juro Sakai
Nature Communications ( Nature Communications ) 13 ( 1 ) 5715 - 5715 2022年12月 [査読有り]
研究論文（学術雑誌） 国際共著
Protein kinase A promotes beige adipogenesis downstream from β-adrenergic receptor signaling by phosphorylating proteins, including histone H3 lysine 9 (H3K9) demethylase JMJD1A. To ensure homeostasis, this process needs to be reversible however, this step is not well understood. We show that myosin phosphatase target subunit 1- protein phosphatase 1β (MYPT1-PP1β) phosphatase activity is inhibited via PKA-dependent phosphorylation, which increases phosphorylated JMJD1A and beige adipogenesis. Mechanistically, MYPT1-PP1β depletion results in JMJD1A-mediated H3K9 demethylation and activation of the Ucp1 enhancer/promoter regions. Interestingly, MYPT1-PP1β also dephosphorylates myosin light chain which regulates actomyosin tension-mediated activation of YAP/TAZ which directly stimulates Ucp1 gene expression. Pre-adipocyte specific Mypt1 deficiency increases cold tolerance with higher Ucp1 levels in subcutaneous white adipose tissues compared to control mice, confirming this regulatory mechanism in vivo. Thus, we have uncovered regulatory cross-talk involved in beige adipogenesis that coordinates epigenetic regulation with direct activation of the mechano-sensitive YAP/TAZ transcriptional co-activators.
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各分野におけるマルチオミクス研究 3.生活習慣病におけるマルチオミクス
松村欣宏, 高橋宙大, 伊藤亮, 米代武司, 米代武司, 稲垣毅, 稲垣毅, 酒井寿郎, 酒井寿郎
実験医学 41 ( 15 ) 2023年
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Yoshihiro Matsumura, Ryo Ito, Ayumu Yajima, Rei Yamaguchi, Toshiya Tanaka, Takeshi Kawamura, Kenta Magoori, Yohei Abe, Aoi Uchida, Takeshi Yoneshiro, Hiroyuki Hirakawa, Ji Zhang, Makoto Arai, Chaoran Yang, Ge Yang, Hiroki Takahashi, Hitomi Fujihashi, Ryo Nakaki, Shogo Yamamoto, Satoshi Ota, Shuichi Tsutsumi, Shin-Ichi Inoue, Hiroshi Kimura, Youichiro Wada, Tatsuhiko Kodama, Takeshi Inagaki, Timothy F Osborne, Hiroyuki Aburatani, Koichi Node, Juro Sakai
Nature Communications ( Nature Communications ) 12 ( 1 ) 2021年12月 [査読有り]
国際共著
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転写促進と抑制の両方のヒストン修飾が共存する新規クロマチンドメインが制御する脂肪細胞分化 (特集 エネルギー代謝調節研究の新展開)
松村 欣宏, 酒井 寿郎
内分泌・糖尿病・代謝内科 = Endocrinology, diabetology & metabolism ( 科学評論社 ) 44 ( 6 ) 425 - 431 2017年06月
◆原著論文【 表示 ／ 非表示 】
◆その他【 表示 ／ 非表示 】
科研費（文科省・学振）獲得実績 【 表示 ／ 非表示 】
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脂肪細胞分化での鍵となるエピゲノムの動的変化の解明
基盤研究(C)
研究期間: 2022年04月 - 2025年03月 代表者: 松村 欣宏
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シグナル感知エピゲノム酵素による世代を超えた環境適応機構の解明
基盤研究(A)
研究期間: 2021年04月 - 2024年03月 代表者: 酒井 寿郎, 米代 武司, 川村 猛, 松村 欣宏
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組織間の情報伝達を記憶するエピゲノム機構の解明
基盤研究(C)
研究期間: 2019年04月 - 2022年03月 代表者: 松村 欣宏
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環境因子とエピゲノム記憶による生活習慣病発症の解明
基盤研究(S)
研究期間: 2016年05月 - 2021年03月 代表者: 酒井 寿郎, 松村 欣宏, 川村 猛
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過栄養による脂肪細胞機能破綻のエピゲノム機構
基盤研究(C)
研究期間: 2016年04月 - 2019年03月 代表者: 松村 欣宏, 川村 猛