Updated on 2024/10/07

Information

 

写真a

 
MIURA SHIZUKA
 
Organization
Medical Institute of Bioregulation Department of Molecular and Cellular Biology Assistant Professor
Title
Assistant Professor
Contact information
メールアドレス
Tel
0926426449
External link

Degree

  • Doctor(medicine)

Research Interests・Research Keywords

  • Research theme:generation of induced fetal intestine derived progenitor cells for medical aplication

    Keyword:regenerative therapy, direct reprogramming, intestinal progenitor cells

    Research period: 2021.10 - 2024.10

Awards

  • 九州大学若手女性研究者・女子大学院生優秀研究者賞 最優秀賞

    2019.10   九州大学  

  • 井上研究奨励賞

    2019.2   井上科学振興財団  

Papers

  • Hepatocytes differentiate into intestinal epithelial cells through a hybrid epithelial/mesenchymal cell state in culture. Reviewed International journal

    Shizuka Miura, Kenichi Horisawa, Tokuko Iwamori, Satoshi Tsujino, Kazuya Inoue, Satsuki Karasawa, Junpei Yamamoto, Yasuyuki Ohkawa, Sayaka Sekiya, Atsushi Suzuki

    Nature communications   15 ( 1 )   3940 - 3940   2024.5   eISSN:2041-1723

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    Hepatocytes play important roles in the liver, but in culture, they immediately lose function and dedifferentiate into progenitor-like cells. Although this unique feature is well-known, the dynamics and mechanisms of hepatocyte dedifferentiation and the differentiation potential of dedifferentiated hepatocytes (dediHeps) require further investigation. Here, we employ a culture system specifically established for hepatic progenitor cells to study hepatocyte dedifferentiation. We found that hepatocytes dedifferentiate with a hybrid epithelial/mesenchymal phenotype, which is required for the induction and maintenance of dediHeps, and exhibit Vimentin-dependent propagation, upon inhibition of the Hippo signaling pathway. The dediHeps re-differentiate into mature hepatocytes by forming aggregates, enabling reconstitution of hepatic tissues in vivo. Moreover, dediHeps have an unexpected differentiation potential into intestinal epithelial cells that can form organoids in three-dimensional culture and reconstitute colonic epithelia after transplantation. This remarkable plasticity will be useful in the study and treatment of intestinal metaplasia and related diseases in the liver.

    DOI: 10.1038/s41467-024-47869-2

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  • Transcription factor-mediated direct cellular reprogramming yields cell-type specific DNA methylation signature Reviewed

    Kenichi Horisawa, Shizuka Miura, Hiromitsu Araki, Fumihito Miura, Takashi Ito, Atsushi Suzuki

    Scientific Reports   13 ( 1 )   22317   2023.12

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    Language:Others   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41598-023-49546-8

  • Secretory GFP reconstitution labeling of neighboring cells interrogates cell–cell interactions in metastatic niches Reviewed

    14 ( 1 )   2023.12

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    Language:Others   Publishing type:Research paper (scientific journal)  

    Abstract

    Cancer cells inevitably interact with neighboring host tissue-resident cells during the process of metastatic colonization, establishing a metastatic niche to fuel their survival, growth, and invasion. However, the underlying mechanisms in the metastatic niche are yet to be fully elucidated owing to the lack of methodologies for comprehensively studying the mechanisms of cell–cell interactions in the niche. Here, we improve a split green fluorescent protein (GFP)-based genetically encoded system to develop secretory glycosylphosphatidylinositol-anchored reconstitution-activated proteins to highlight intercellular connections (sGRAPHIC) for efficient fluorescent labeling of tissue-resident cells that neighbor on and putatively interact with cancer cells in deep tissues. The sGRAPHIC system enables the isolation of metastatic niche-associated tissue-resident cells for their characterization using a single-cell RNA sequencing platform. We use this sGRAPHIC-leveraged transcriptomic platform to uncover gene expression patterns in metastatic niche-associated hepatocytes in a murine model of liver metastasis. Among the marker genes of metastatic niche-associated hepatocytes, we identify Lgals3, encoding galectin-3, as a potential pro-metastatic factor that accelerates metastatic growth and invasion.

    DOI: 10.1038/s41467-023-43855-2

  • Direct reprogramming of human umbilical vein- and peripheral blood-derived endothelial cells into hepatic progenitor cells. Reviewed International journal

    Hiroki Inada, Miyako Udono, Kanae Matsuda-Ito, Kenichi Horisawa, Yasuyuki Ohkawa, Shizuka Miura, Takeshi Goya, Junpei Yamamoto, Masao Nagasaki, Kazuko Ueno, Daisuke Saitou, Mikita Suyama, Yoshihiko Maehara, Wataru Kumamaru, Yoshihiro Ogawa, Sayaka Sekiya, Atsushi Suzuki

    Nature communications   11 ( 1 )   5292 - 5292   2020.10

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41467-020-19041-z

  • Direct Lineage Reprogramming of Mouse Fibroblasts to Acquire the Identity of Fetal Intestine-Derived Progenitor Cells. Reviewed International journal

    Shizuka Miura, Atsushi Suzuki

    Methods in molecular biology (Clifton, N.J.)   2171   231 - 236   2020.9

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/978-1-0716-0747-3_14

  • Induction of Steatohepatitis and Liver Tumorigenesis by Enforced Snail Expression in Hepatocytes Reviewed

    Shizuka Miura, Atsushi Suzuki

    The American Journal of Pathology   190 ( 6 )   1271 - 1283   2020.6

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.ajpath.2020.02.005

    Repository Public URL: https://hdl.handle.net/2324/7173546

  • Cell Aggregation Culture Induces Functional Differentiation of Induced Hepatocyte-like Cells through Activation of Hippo Signaling. Reviewed International journal

    Junpei Yamamoto, Miyako Udono, Shizuka Miura, Sayaka Sekiya, Atsushi Suzuki

    Cell reports   25 ( 1 )   183 - 198   2018.10

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.celrep.2018.09.010

  • Brief summary of the current protocols for generating intestinal organoids Reviewed

    Shizuka Miura, Atsushi Suzuki

    Development Growth and Differentiation   60   387 - 392   2018.8

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    Brief summary of the current protocols for generating intestinal organoids
    © 2018 Japanese Society of Developmental Biologists The intestine has fundamental functions for the maintenance of homeostasis, including food digestion and nutrient/water absorption. Although the lumen of the intestine is always exposed to pathogens, intestinal epithelial cells form monolayer sheets that act as an epithelial barrier to prevent the invasion of pathogens. Thus, disruption of the intestinal epithelial barrier causes inflammatory bowel diseases. To investigate the details of these intractable intestinal diseases, it is necessary to analyze the characteristics of intestinal epithelial cells in vitro. However, it is difficult to maintain and propagate intestinal epithelial cells in culture. Recently, intestinal organoid culture systems have been established, in which differentiated intestinal epithelial lineage cells can be continuously produced from intestinal stem cells and form epithelial organoids with crypt-like structures in long-term culture. Moreover, intestinal epithelial organoids can be generated not only from intestinal tissue-derived cells, embryonic stem cells, and induced pluripotent stem cells, but also by inducing direct conversion of nonintestinal somatic cells into intestinal epithelial cells. These intestinal organoids can be used in basic studies for understanding the mechanisms underlying intestinal development and diseases and will be applied in future transplantation therapy and drug discovery to treat intestinal diseases.

    DOI: 10.1111/dgd.12559

  • Generation of Mouse and Human Organoid-Forming Intestinal Progenitor Cells by Direct Lineage Reprogramming Reviewed

    Shizuka Miura, Atsushi Suzuki

    CELL STEM CELL   21 ( 4 )   456 - +   2017.10

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.stem.2017.08.020

    Repository Public URL: https://hdl.handle.net/2324/7172621

  • Myofibroblasts Derived from Hepatic Progenitor Cells Create the Tumor Microenvironment Reviewed

    Sayaka Sekiya, Shizuka Miura, Kanae Matsuda-Ito, Atsushi Suzuki

    STEM CELL REPORTS   7 ( 6 )   1130 - 1139   2016.12

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.stemcr.2016.11.002

  • Kupffer cells induce Notch-mediated hepatocyte conversion in a common mouse model of intrahepatic cholangiocarcinoma Reviewed

    Maiko Terada, Kenichi Horisawa, Shizuka Miura, Yasuo Takashima, Yasuyuki Ohkawa, Sayaka Sekiya, Kanae Matsuda-Ito, Atsushi Suzuki

    SCIENTIFIC REPORTS   6   2016.10

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/srep34691

  • Suppression of lethal-7b and miR-125a/b Maturation by Lin28b Enables Maintenance of Stem Cell Properties in Hepatoblasts Reviewed

    Yasuo Takashima, Maiko Terada, Miyako Udono, Shizuka Miura, Junpei Yamamoto, Atsushi Suzuki

    HEPATOLOGY   64 ( 1 )   245 - 260   2016.7

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/hep.28548

  • Rapid cell-fate conversion of mouse fibroblasts into hepatocyte-like cells Reviewed

    Miura Shizuka, Suzuki Atsushi

    Inflammation and Regeneration   34 ( 5 )   211 - 216   2014.11

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    Language:English  

    Rapid cell-fate conversion of mouse fibroblasts into hepatocyte-like cells
    Recent progress in studies on direct cell-fate conversion of differentiated somatic cells into other cell types, which is known as "direct reprogramming", is expected to lead to innovations in health care. In our previous study, we found that three specific combinations of two transcription factors, comprising Hnf4α plus Foxa1, Foxa2, or Foxa3, were able to induce conversion of mouse fibroblasts into functional hepatocyte-like cells. These induced hepatocyte-like (iHep) cells will be useful for developing regenerative therapies for liver diseases and examining the pharmacological effects of drugs. However, to evaluate the potential utility of iHep cells, the phenomena involved in the direct conversion of fibroblasts into iHep cells should be examined in detail. Thus, in this study, we sequentially analyzed the early stage of fibroblast conversion into iHep cells after infection with retroviruses expressing Hnf4α and Foxa3. Our data demonstrated that the conversion into iHep cells began within 2 days after introduction of the transgenes into fibroblasts, and the number of iHep cells increased gradually as the culture progressed. The rapid cell-fate conversion of fibroblasts into iHep cells and stable expansion of iHep cells are two pieces of evidence suggesting the utility of iHep cells for cell transplantation therapy, bioartificial liver development, and screening of drugs for patients with liver diseases, which require many hepatocytes within a short period of time.

    DOI: 10.2492/inflammregen.34.211

  • Acquisition of lipid metabolic capability in hepatocyte-like cells directly induced from mouse fibroblasts. Reviewed

    Miura S, Suzuki A

    Frontiers in cell and developmental biology   2   43   2014.8

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    Acquisition of lipid metabolic capability in hepatocyte-like cells directly induced from mouse fibroblasts.

    DOI: 10.3389/fcell.2014.00043

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Presentations

  • 肝細胞誘導におけるリプログラミング過程の観察と解析

    三浦静, 関谷明香, 鈴木淳史

    第19回肝細胞研究会  2012.6 

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    Language:Japanese  

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  • 肝細胞におけるsnailの過剰発現は肝細胞癌を誘導する

    三浦静, 鈴木淳史

    第25回肝細胞研究会  2018.7 

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    Language:Japanese  

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  • ダイレクトリプログラミングによるオルガノイド形成能を有するマウスおよびヒト腸前駆細胞の作製

    三浦静, 鈴木淳史

    第17回日本再生医療学会  2018.3 

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    Language:Japanese  

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  • Overexpression of transcription factor Snail induces liver tumor formation: International conference

    Keystone symposia  2016.3 

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    Overexpression of transcription factor Snail induces liver tumor formation:

  • iHep細胞研究から見出された肝細胞分化の新規制御機構

    三浦静, 鈴木淳史

    第14回日本再生医療学会総会  2015.3 

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    Language:Japanese  

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  • iHep細胞研究から見出された肝細胞分化の新規制御機構

    三浦静, 関谷明香, 鈴木淳史

    第21回肝細胞研究会  2014.6 

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  • Analysis of hepatic lipid metabolism using iHep cells International conference

    2013.11 

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    Analysis of hepatic lipid metabolism using iHep cells

  • Analysis of reprogramming process from fibroblasts to induced hepatocyte-like cells International conference

    Epithelial tubulology  2013.6 

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    Analysis of reprogramming process from fibroblasts to induced hepatocyte-like cells

  • iHep細胞を用いた脂質代謝機能の解析

    三浦静, 鈴木淳史

    第36回日本分子生物学会  2013.12 

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  • nalysis of hepatic lipid metabolism using iHep cells International conference

    The 20th Annual Meeting of the Japanese Society for the Research of Hepatic Cells  2013.9 

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    nalysis of hepatic lipid metabolism using iHep cells

  • Induction of functional hepatocytes from mouse fibroblasts Invited International conference

    The International Liver Congress by EASL  2012.4 

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    Induction of functional hepatocytes from mouse fibroblasts

  • 肝細胞誘導におけるリプログラミング過程の観察と解析

    三浦静, 関谷明香, 鈴木淳史

    第35回日本分子生物学会  2012.12 

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    Language:Japanese  

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Professional Memberships

  • 再生医療学会

  • 分子生物学会

  • 肝細胞研究会

Research Projects

  • ダイレクトリプログラミングを利用したヒト食道上皮細胞の作製

    Grant number:23K17199  2023 - 2024

    日本学術振興会  科学研究費助成事業  若手研究

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    Authorship:Principal investigator  Grant type:Scientific research funding

  • ダイレクトリプログラミングによる血液由来腸前駆細胞の作製

    Grant number:21K18039  2021 - 2023

    日本学術振興会  科学研究費助成事業  若手研究

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    Authorship:Principal investigator  Grant type:Scientific research funding

  • 腸前駆細胞直接誘導法を利用したヒト成体型腸上皮オルガノイドの作製

    2018 - 2019

    科学研究費助成事業  若手研究(スタートアップ)

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    Authorship:Principal investigator  Grant type:Scientific research funding

  • ダイレクトリプログラミングによるヒト腸幹細胞の作製

    Grant number:16J02459  2016 - 2017

    日本学術振興会  科学研究費助成事業  特別研究員奨励費

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    Grant type:Scientific research funding

Social Activities

  • 九州大学病院【サイエンスカフェ 】ジェネティック・クエスト Episode2: あなたの大切な「生命」のクローンを作りたいですか?

    九州大学病院 臨床遺伝医療部  九州大学  2024.2

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    Audience: General, Scientific, Company, Civic organization, Governmental agency

    Type:Lecture