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Affiliation |
Graduate School of Medicine Doctorial Course in Medicine Bioregulatory Medicine Department of Biochemistry and Metabolic Science |
MATSUMURA Yoshihiro
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Research Interests 【 display / non-display 】
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Epigenetics
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Adipocytes
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Metabolism
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Next generation sequencing
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Histone modifications
Graduating School 【 display / non-display 】
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-1998.03
Tohoku University Graduated
Graduate School 【 display / non-display 】
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-2004.03
Tohoku University Graduate School, Division of Natural Science Department of Chemistry Doctor's Course Completed
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-2002.03
Tohoku University Graduate School, Division of Natural Science Department of Chemistry Master's Course Completed
Studying abroad experiences 【 display / non-display 】
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2008.01-2011.08
Oregon Health Science University Postdoctoral researcher
Campus Career 【 display / non-display 】
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2023.11-Now
Akita University Graduate School of Medicine Doctorial Course in Medicine Bioregulatory Medicine Department of Biochemistry and Metabolic Science Professor
External Career 【 display / non-display 】
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2022.04-2023.10
Tohoku University Graduate School of Medicine Associate Professor
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2017.04-2022.03
The University of Tokyo Research Center for Advanced Science and Technology, Division of Metabolic Medicine Associate Professor
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2012.04-2017.03
The University of Tokyo Research Center for Advanced Science and Technology, Division of Metabolic Medicine Research Associate
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2011.04-2012.03
The University of Tokyo Research Center for Advanced Science and Technology, Division of Metabolic Medicine Appointed Research Associate
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2004.06-2008.01
Akita University Faculty of Medicine Postdoctoral Researcher
Research Areas 【 display / non-display 】
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Life Science / System genome science / Epigenetics, Next generation sequencing
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Life Science / Molecular biology / Histone modifications, RNA modifications
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Life Science / Metabolism and endocrinology / Metabolism, Adipocytes
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Life Science / Cell biology
Research Achievements 【 display / non-display 】
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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 2023.11 [Refereed]
Research paper (journal) Domestic Co-author
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 2023.10 [Refereed]
Research paper (journal) Domestic Co-author
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 2023.03 [Refereed]
Research paper (journal) Domestic Co-author
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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Osawa T, Shimamura T, Saito K, Hasegawa Y, Ishii N, Nishida M, Ando R, Kondo A, Anwar M, Tsuchida R, Hino S, Sakamoto A, Igarashi K, Saitoh K, Kato K, Endo K, Yamano S, Kanki Y, Matsumura Y, Minami T, Tanaka T, Anai M, Wada Y, Wanibuchi H, Hayashi M, Hamada A, Yoshida M, Yachida S, Nakao M, Sakai J, Aburatani H, Shibuya M, Hanada K, Miyano S, Soga T, Kodama T
Cell Reports 29 ( 1 ) 89 - 103.e7 2019.10 [Refereed]
Research paper (journal) Domestic Co-author
Tolerance to severe tumor microenvironments, including hypoxia and nutrient starvation, is a common feature of aggressive cancer cells and can be targeted. However, metabolic alterations that support cancer cells upon nutrient starvation are not well understood. Here, by comprehensive metabolome analyses, we show that glutamine deprivation leads to phosphoethanolamine (PEtn) accumulation in cancer cells via the downregulation of PEtn cytidylyltransferase (PCYT2), a rate-limiting enzyme of phosphatidylethanolamine biosynthesis. PEtn accumulation correlated with tumor growth under nutrient starvation. PCYT2 suppression was partially mediated by downregulation of the transcription factor ELF3. Furthermore, PCYT2 overexpression reduced PEtn levels and tumor growth. In addition, PEtn accumulation and PCYT2 downregulation in human breast tumors correlated with poor prognosis. Thus, we show that glutamine deprivation leads to tumor progression by regulating PE biosynthesis via the ELF3-PCYT2 axis. Furthermore, manipulating glutamine-responsive genes could be a therapeutic approach to limit cancer progression.
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Nagai N, Ohguchi H, Nakaki R, Matsumura Y, Kanki Y, Sakai J, Aburatani H, Minami T
PLoS Genetics 14 ( 11 ) e1007826 2018.11 [Refereed]
Research paper (journal) Domestic Co-author
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Multi-omics in lifestyle-related diseases
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
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Discovery of non-canonical bivalent chromatin that regulates Adipogenic master regulator genes
44 ( 6 ) 425 - 431 2017.06
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Metabolic syndrome and Epigenome
49 ( 2 ) 56 - 62 2017.02
◆Original paper【 display / non-display 】
◆Other【 display / non-display 】
Grant-in-Aid for Scientific Research 【 display / non-display 】
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Elucidation of epigenome dynamics that determines adipocyte differentiation
Grant-in-Aid for Scientific Research(C)
Project Year： 2022.04 - 2025.03
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Grant-in-Aid for Scientific Research(A)
Project Year： 2021.04 - 2024.03
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Elucidation of epigenetic mechanisms that memorize inter-tissue communication
Grant-in-Aid for Scientific Research(C)
Project Year： 2019.04 - 2022.03 Investigator(s): Matsumura Yoshihiro
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Elucidation of lifestyle-related diseases development due to environmental factors and epigenetic memory
Grant-in-Aid for Scientific Research(S)
Project Year： 2016.05 - 2021.03 Investigator(s): SAKAI Juro
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Epigenetic mechanism of adipocyte dysfunction under overnutrition
Grant-in-Aid for Scientific Research(C)
Project Year： 2016.04 - 2019.03 Investigator(s): Matsumura Yoshihiro, Kawamura Takeshi