Updated on 2025/07/19

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写真a

 
Tadaaki Nakajima
 
Organization
Graduate School of Nanobioscience Department of Life and Environmental System Science Assistant Professor
School of Science Department of Science
Title
Assistant Professor
Contact information
メールアドレス
Profile

・RNA-seqやChIP-seqのデータを元にin silicoで解析することで、シグナルネットワーク上の重要な因子を発見する。

・細胞をピースに見立てたボトムアップ組織工学技術を用いて、in vitroのデバイス上の生体高分子を足場として、上皮細胞や間葉系細胞を自由に配置し、三次元組織モデルを構築する。

・in vivoの生体分子の局在や物理パラメータと比較する。

上記in silico, in vitro, in vivoにおける研究を融合することで、自在に組織をデザインする、デザイン組織工学手法を用いて、上皮・間質・筋層の立体構造形成の共通法則を発見することを目的としている。

主に、同一原基であるミュラー管より発生する、卵管、子宮、膣の運命決定機構の解明を試みている。同時に、in vitroで子宮の生理現象や着床現象を「見える化」することに挑戦している。

External link

Degree

  • 博士 (理学) ( 2012.3   横浜市立大学 )

Research Interests

  • 平滑筋層

  • 組織立体構造

  • バイオエンジニアリング

  • デザイン組織工学

  • 卵管

  • 組織学

  • 内分泌学

  • Müllerian duct

  • 発生工学

  • vagina

  • uterus

Research Areas

  • Manufacturing Technology (Mechanical Engineering, Electrical and Electronic Engineering, Chemical Engineering) / Biofunction and bioprocess engineering

  • Life Science / Morphology and anatomical structure

Education

  • Yokohama City University   Graduate   Graduate School of Nanobioscience

    2009.4 - 2012.3

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  • Yokohama City University   Graduate

    2007.4 - 2009.3

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  • Yokohama City University

    2003.4 - 2007.3

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Research History

  • Yokohama City University   School of Science   Assistant Professor

    2021.4

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    Country：Japan

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  • The University of Tokyo   Institute of Industrial Science

    2018.8 - 2021.3

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  • The University of Tokyo   Institute of Industrial Science

    2018.5 - 2018.8

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  • Yokohama City University   Graduate School of Nanobioscience, Graduate

    2018.4

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  • Tokyo University of Science   Faculty of Industrial Science and Technology, Biological Science and Technology

    2014.4 - 2018.3

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  • Tokyo University of Science   Faculty of Industrial Science and Technology, Biological Science and Technology

    2013.4 - 2014.3

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  • Japan Women's University   Faculty of Science, Department of Chemical and Biological Sciences

    2012.4 - 2014.3

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  • Yokohama City University   Graduate School of Nanobioscience, Graduate

    2012.4 - 2013.3

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  • Yokohama City University   Graduate School of Nanobioscience, Graduate

    2011.4 - 2012.3

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Professional Memberships

  • 日本比較内分泌学会

    2023.6

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  • Society for the Study of Reproduction

    2017.5

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  • THE ZOOLOGICAL SOCIETY OF JAPAN

    2007.4

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  • THE JAPANESE SOCIETY FOR BIOMATERIALS

    2016.4 - 2018.3

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Papers

  • Deficiency of Estrogen Receptor 2 Expression Enhances Disorganization of the Mouse Uterus With Age Reviewed

    Tadaaki Nakajima, Reina Arakawa, Saki Nose, Norika Matsuda, Airi Tsuge, Mami Ishii, Tomohiro Ishikawa, Yurika Tsurugai, Shinichi Miyagawa, Taisen Iguchi, Tomomi Sato

    Endocrinology   166 ( 8 )   2025.6

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Endocrine Society  

    Abstract

    Constitutive stimulation of estrogen signaling in mice causes dilated uterine glands with activation of epithelial cell proliferation. In estrogen receptor β knockout (Esr2 KO) mice, cell proliferation in the uterine epithelium is permanently stimulated; therefore, we histologically analyzed the uterine structure in Esr2 KO mice with age. In the uterus of Esr2 KO mice, dilation of the uterine glands was accelerated and the collagen was accumulated in the stroma. The uterine glands were dilated with age even in wild-type (WT) mice; however, Esr2 KO accelerated the dilation of uterine glands quantitatively. The expression of FOXA2 transcription factor, which is essential for uterine glandular function, was diminished in dilated uterine glands of WT and Esr2 KO mice and decreased in the uterine glands of normal size in 12-month-old Esr2 KO mice. To investigate mechanisms of the collagen accumulation in the Esr2 KO uterus, we focused on collagen synthesis and degradation. In the uterine stroma of Esr2 KO mice, MMP8 expression in whole uteri and the number of MMP8-expressing macrophages were decreased. An analysis of the comprehensive gene expression suggested that increased expression of fibroblast growth factors and decreased expression of an aquaporin may be related to the dilation of uterine glands in Esr2 KO mice, and reduced infiltration or differentiation into the macrophages with MMP8 expression may be involved with the collagen accumulation in Esr2 KO mice with age. Taken together, the absence of ESR2 constitutively disrupts estrogen signaling and promotes aging in the uterus via stimulation of epithelial cell proliferation and a decrease of MMP8-expressing macrophages.

    DOI： 10.1210/endocr/bqaf103

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    Other Link： https://academic.oup.com/endo/article-pdf/166/8/bqaf103/63422160/bqaf103.pdf

  • In silico screening system based on a transcription factors regulatory network only using transcriptomic data Reviewed

    Tadaaki Nakajima, Kentaro Harada, Yasuhiro Tomooka, Tomomi Sato

    PLOS ONE   20 ( 4 )   e0319971 - e0319971   2025.4

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    Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science (PLoS)  

    In this study, we developed a method to identify core transcription factors (TFs) involved in differentiation using only comprehensive gene analysis. The theory of in silico screening using TFs regulatory network analysis (ISNA) required the following requirements: (1) estimating promoter regions, (2) constructing TFs regulatory network (TRN) relationships using the nucleotide sequence information in the promoters and score matrices derived from TF consensus sequences, and (3) identifying candidate core TFs by determining dissociation constants (K<sub>d</sub> values) within the relationships of TRN. ISNA demonstrated the ability to predict the core TFs involved in the endothelial-to-mesenchymal transition of human umbilical vein endothelial cell (HUVEC) and the differentiation of human embryonic stem cells into mesodermal cells. Using ISNA, we identified HMGA2 as a novel core TF in uterine epithelium. Notably, HMGA2 expression was predominantly detected in uterine epithelium, where it regulated cell proliferation in response to estrogen. These findings highlight ISNA’s potential to identify core TFs based on transcriptomic data.

    DOI： 10.1371/journal.pone.0319971

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  • Intraluminal pressure triggers a rapid and persistent reinforcement of endothelial barriers Reviewed

    Aurélien Bancaud, Tadaaki Nakajima, Jun-Ichi Suehiro, Baptiste Alric, Florent Morfoisse, Jean Cacheux, Yukiko T. Matsunaga

    Lab on a Chip   2025.1

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    Language：English   Publisher：Cold Spring Harbor Laboratory  

    Abstract

    In response to mechanical cues, endothelial cells elicit highly sensitive cellular response pathways that contribute to the regulation of the physiology and disorders of the vascular system. However, it remains relatively unexplored how endothelial tissues process and integrate the intraluminal pressure, and in turn regulate the permeation flow across the vessel wall. Leveraging a tissue engineering approach to create microvessels (MVs), we measured real-time permeation flow induced by intraluminal pressures ranging from 0.1 to 2.0 kPa. Our findings reveal that mechanically stimulated MVs strengthen their barrier function within seconds of exposure to pressures below 1 kPa, with this enhanced barrier function persisting for 30 minutes. We demonstrate that this barrier reinforcement is linked to the closure of paracellular gaps. Additionally, we observe that it is associated with, and depends on, actin cytoskeleton reorganization, including the accumulation of stress fibers near intercellular junctions and the broadening of adherence junction protein localization. These findings provide insights into the ability of endothelial tissues to regulate interstitial fluid flow in response to sudden increases in blood pressure.

    DOI： 10.1101/2025.01.22.634268

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  • Photodynamic Effect of Amphiphilic N<sup>∧</sup>C<sup>∧</sup>N-Coordinated Platinum(II) Complexes in Human Umbilical Vein Endothelial Cells Reviewed

    Shingo Hattori, Mizuki Ogishima, Tadaaki Nakajima, Shota Hosoya, Yuichi Kitagawa, Yasuchika Hasegawa, Shinji Nonose, Tomomi Sato, Kazuteru Shinozaki

    Inorganic Chemistry   2024.7

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

    DOI： 10.1021/acs.inorgchem.4c01414

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  • Protocol for fabricating and characterizing microvessel-on-a-chip for human umbilical vein endothelial cells Reviewed

    Jean Cacheux, Tadaaki Nakajima, Daniel Alcaide, Takanori Sano, Kotaro Doi, Aurélien Bancaud, Yukiko T. Matsunaga

    STAR Protocols   5 ( 2 )   102950 - 102950   2024.6

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.xpro.2024.102950

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  • SMAD2/3 signaling regulates initiation of mouse Wolffian ducts and proximal differentiation in Müllerian ducts Reviewed

    Tadaaki Nakajima, Akihiro Imai, Chihiro Ishii, Kota Tsuruyama, Risa Yamanaka, Yasuhiro Tomooka, Shinta Saito, Noritaka Adachi, Satomi Kohno, Tomomi Sato

    FEBS Open Bio   2023.11

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    Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

    Male and female reproductive tracts develop from anterior intermediate mesoderm with similar differentiation processes. The anterior intermediate mesoderm develops into the mesonephros, and the Wolffian duct initiates by epithelialization in the mesonephros. The Müllerian duct invaginates from the coelomic epithelium of the cranial mesonephros for ductal formation and is then regionalized into proximal to caudal female reproductive tracts. In this study, we focused on the epithelialization of the Wolffian duct, initiation of the Müllerian duct, and the regionalization step of the Müllerian ducts as a continuous process. By using intermediate mesodermal cells from mouse pluripotent stem cells, we identified that inhibition of SMAD2/3 signaling might be involved in the differentiation into mesenchymal cells, after which mesonephric cells might be then epithelialized during differentiation of the Wolffian duct. Aggregation of coelomic epithelial cells might be related to initiation of the Müllerian duct. Transcriptomic analysis predicted that consensus sequences of SMAD3/4 were enriched among highly expressed genes in the proximal Müllerian duct. SMAD2/3 signaling to regulate differentiation of the Wolffian duct was continuously activated in the proximal Müllerian duct and was involved in proximal and oviductal regionalization. Therefore, SMAD2/3 signaling may be finely tuned to regulate differentiation from initiation to regionalization steps.

    DOI： 10.1002/2211-5463.13729

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  • Image-based crosstalk analysis of cell–cell interactions during sprouting angiogenesis using blood-vessel-on-a-chip Reviewed

    Takanori Sano, Tadaaki Nakajima, Koharu Alicia Senda, Shizuka Nakano, Mizuho Yamato, Yukinori Ikeda, Hedele Zeng, Jun-ichi Kawabe, Yukiko T. Matsunaga

    Stem Cell Research &amp; Therapy   13 ( 1 )   2022.12

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    Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

    Abstract

    Background

    Sprouting angiogenesis is an important mechanism for morphogenetic phenomena, including organ development, wound healing, and tissue regeneration. In regenerative medicine, therapeutic angiogenesis is a clinical solution for recovery from ischemic diseases. Mesenchymal stem cells (MSCs) have been clinically used given their pro-angiogenic effects. MSCs are reported to promote angiogenesis by differentiating into pericytes or other vascular cells or through cell–cell communication using multiple protein–protein interactions. However, how MSCs physically contact and move around ECs to keep the sprouting angiogenesis active remains unknown.

    Methods

    We proposed a novel framework of EC–MSC crosstalk analysis using human umbilical vein endothelial cells (HUVECs) and MSCs obtained from mice subcutaneous adipose tissue on a 3D in vitro model, microvessel-on-a-chip, which allows cell-to-tissue level study. The microvessels were fabricated and cultured for 10 days in a collagen matrix where MSCs were embedded.

    Results

    Immunofluorescence imaging using a confocal laser microscope showed that MSCs smoothed the surface of the microvessel and elongated the angiogenic sprouts by binding to the microvessel’s specific microstructures. Additionally, three-dimensional modeling of HUVEC–MSC intersections revealed that MSCs were selectively located around protrusions or roots of angiogenic sprouts, whose surface curvature was excessively low or high, respectively.

    Conclusions

    The combination of our microvessel-on-a-chip system for 3D co-culture and image-based crosstalk analysis demonstrated that MSCs are selectively localized to concave–convex surfaces on scaffold structures and that they are responsible for the activation and stabilization of capillary vessels.

    DOI： 10.1186/s13287-022-03223-1

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    Other Link： https://link.springer.com/article/10.1186/s13287-022-03223-1/fulltext.html

  • Nailfold capillary patterns correlate with age, gender, lifestyle habits, and fingertip temperature Reviewed

    Tadaaki Nakajima, Shizuka Nakano, Akihiko Kikuchi, Yukiko T. Matsunaga

    PLOS ONE   17 ( 6 )   e0269661 - e0269661   2022.6

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    Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science (PLoS)  

    Nailfold capillaroscopy is a simple and noninvasive imaging tool to visualize the pattern of capillaries. Microvascular abnormalities have been previously observed in autoimmune disease such as systemic sclerosis and diabetes. Thus, early detection of microvascular dysfunction or changes has promising way for the one of the disease preventions. In this study, for routine health checkups, we evaluated the relationship between the structure of nailfold capillaries and lifestyle habits in healthy participants. First, we analyzed the correlation of structural parameters of nailfold capillaries with values of responses to questions on their lifestyle habits in 224 participants. The results suggested that an unhealthy lifestyle, including poor sleeping habits, smoking, intense exercise, and drinking alcohol, causes a change in the pattern of nailfold capillaries. We then investigated whether the pattern of nailfold capillaries changed after a conscious improvement in lifestyle habits. One to two weeks after the self-improvement of lifestyle habits, the hairpin loops sharpened or straightened. In conclusion, this study is the first report indicating a correlation between the structure of nailfold capillaries and lifestyle habits in a non-clinical population. The simple, inexpensive, and noninvasive method using nailfold microscopy can be employed for routine health checkups everywhere even at a bedside.

    DOI： 10.1371/journal.pone.0269661

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  • Cell culture and genetic transfection methods for the Japanese scallop, Patinopecten yessoensis Reviewed

    Minako Suzuki, Tomomi Okumura, Koki Uchida, Yukinori Ikeda, Yasuhiro Tomooka, Tadaaki Nakajima

    FEBS Open Bio   2021.7

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    Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

    DOI： 10.1002/2211-5463.13237

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    Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/2211-5463.13237

  • Extra cellular matrix components and elasticity regulate mouse vaginal epithelial differentiation induced by mesenchymal cells Reviewed

    Tadaaki Nakajima, Miyabi Kozuma, Tomoko Hirasawa, Yukiko T Matsunaga, Yasuhiro Tomooka

    Biology of Reproduction   2021.3

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    Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

    <title>Abstract</title>
    Oviduct, uterus, and vagina are derived from Müllerian ducts. But only in the vagina, the epithelium differentiates into stratified layers. Organ-specific secreted factors derived from the stroma of a neonatal mouse induce epithelial differentiation in the female reproductive tracts. However, the effects of the components and mechanical property of extracellular matrix (ECM) on the regulation of gene expression in the mesenchymal cells of neonatal stroma and differentiation of epithelium in the female reproductive tracts have been overlooked. In the present study, we have developed a simple 3D neonatal vaginal model using clonal cell lines to study the effect of ECM's components and stiffness on the epithelial stratification. Transcriptome analysis was performed by DNA-microarray to identify the components of ECM involved in the differentiation of vaginal epithelial stratification. The knockdown experiment of the candidate genes relating to vaginal epithelial stratification was focused on fibromodulin (Fmod), a collagen cross-linking protein. FMOD was essential for the expression of Bmp4, which encodes secreted factors to induce the epithelial stratification of vaginal mesenchymal cells. Furthermore, stiffer ECM as a scaffold for epithelial cells is necessary for vaginal epithelial stratification. Therefore, the components and stiffness of ECM are both crucial for the epithelial stratification in the neonatal vagina.

    DOI： 10.1093/biolre/ioab041

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  • A simple three-dimensional gut model constructed in a restricted ductal microspace induces intestinal epithelial cell integrity and facilitates absorption assays Reviewed

    Tadaaki Nakajima, Katsunori Sasaki, Akihiro Yamamori, Kengo Sakurai, Kaori Miyata, Tomoyuki Watanabe, Yukiko T. Matsunaga

    Biomaterials Science   8 ( 20 )   5615 - 5627   2020.8

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Royal Society of Chemistry (RSC)  

    <p>A new 3D gut-on-a-chip on a ductal scaffold induced a differentiated epithelial layer and allowed permeability and absorption assay.</p>

    DOI： 10.1039/d0bm00763c

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  • Developmental mechanisms regulating the formation of smooth muscle layers in the mouse uterus Reviewed

    Tadaaki Nakajima, Naoto Sakai, Miho Nogimura, Yasuhiro Tomooka

    Biology of Reproduction   2020.6

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    Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

    <title>Abstract</title>
    Uterine smooth muscle cells differentiate from mesenchymal cells, and gap junctions connect the muscle cells in the myometrium. At the neonatal stage, a uterine smooth muscle layer is situated away from the epithelium when smooth muscle cells are grafted near the epithelium, suggesting that the epithelium plays an important role in differentiation, proliferation, and/or migration of smooth muscle cells. In this study, developmental mechanisms regulating the formation of the smooth muscle layers in the mouse uterus were analyzed using an in vitro culture model. Differentiation of smooth muscle cells occurs at a neonatal stage because ACTA2 gene expression was increased at the outer layer, and GJA1 was not expressed in cellular membranes of uterine smooth muscle cells by postnatal day 15. To analyze the effects of the epithelium on the differentiation of smooth muscle cells, a bulk uterine mesenchymal cell line was established from p53−/− mice at postnatal day 3 (P3US cells). Co-culture with Müllerian ductal epithelial cells (E1 cells) induced repulsive migration of ACTA2-positive cells among bulk P3US cells from E1 cells, but it had no effects on the migration of any of 100% ACTA2-positive or negative smooth muscle cell lines cloned from P3US cells. Thus, uterine epithelial cells indirectly affected the repulsive migration of smooth muscle cells via mesenchymal cells. Conditioned medium by E1 cells inhibited differentiation into smooth muscle cells of clonal cells established from P3US cells. Therefore, the uterine epithelium inhibits the differentiation of stem-like progenitor mesenchymal cells adjacent to the epithelium into smooth muscle cells.

    DOI： 10.1093/biolre/ioaa104

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  • Retinoic acid signaling determines the fate of the uterus from the mouse Müllerian duct. Reviewed

    Nakajima T, Sato T, Iguchi T, Takasugi N

    Reproductive toxicology (Elmsford, N.Y.)   86   56 - 61   2019.6

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  • Elongation of Müllerian ducts and connection to urogenital sinus determine the borderline of uterine and vaginal development. Reviewed

    Nakajima T, Yamanaka R, Tomooka Y

    Biochemistry and biophysics reports   17   44 - 50   2019.3

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  • Efficacy of Fibroblast Growth Factor on Epithelialization of the Neovagina in Patients with Mayer-Rokitansky-Kuster-Hauser Syndrome Who Underwent Vaginoplasty Reviewed

    Tomoko Nagata, Aiko Kawano, Makiko Koyama, Tomomi Nakamura, Fumiki Hirahara, Tadaaki Nakajima, Tomomi Sato, Hideya Sakakibara

    JOURNAL OF PEDIATRIC AND ADOLESCENT GYNECOLOGY   30 ( 3 )   400 - 404   2017.6

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

    DOI： 10.1016/j.jpag.2015.12.001

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  • Retinoic acid signaling determines the fate of uterine stroma in the mouse Mullerian duct Reviewed

    Tadaaki Nakajima, Taisen Iguchi, Tomomi Sato

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   113 ( 50 )   14354 - 14359   2016.12

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

    DOI： 10.1073/pnas.1608808113

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  • Neonatal Estrogen Receptor beta Is Important in the Permanent Inhibition of Epithelial Cell Proliferation in the Mouse Uterus Reviewed

    Tadaaki Nakajima, Yuki Tanimoto, Masami Tanaka, Pierre Chambon, Hajime Watanabe, Taisen Iguchi, Tomomi Sato

    ENDOCRINOLOGY   156 ( 9 )   3317 - 3328   2015.9

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

    DOI： 10.1210/en.2015-1012

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  • Fucosylated heparan sulfate from the midgut gland of Patinopecten yessoensis Reviewed

    Shoichi Onishi, Kento Shionoya, Kazuki Sato, Ayumu Mubuchi, Shiori Maruyama, Tadaaki Nakajima, Masahiro Komeno, Shinji Miyata, Kazumi Yoshizawa, Takeshi Wada, Robert J. Linhardt, Toshihiko Toida, Kyohei Higashi

    Carbohydrate Polymers   313   120847 - 120847   2023.8

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.carbpol.2023.120847

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  • 壁細胞を有する三次元人工微小血管モデルを用いたヒハツエキス，イチョウ葉エキス配合食品の血管透過性に対する評価

    桜庭 大樹, 中島 忠章, 阿部 卓哉, 二階堂 沙紀, 山口芳正, 佐野貴規, 松永行子

    生産研究   75 ( 1 )   111 - 114   2023.2

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    Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)  

    DOI： 10.11188/seisankenkyu.75.111

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  • Design of a Sensitive Extracellular Vesicle Detection Method Utilizing a Surface-Functionalized Power-Free Microchip Reviewed

    Ishihara R, Katagiri A, Nakajima T, Matsui R, Hosokawa K, Maeda M, Tomooka Y, Kikuchi A

    12 ( 679 )   2022.6

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    Language：English  

    DOI： 10.3390/membranes12070679

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  • The Ccl17 gene encoding TARC is synergistically transactivated by PU.1 and IRF4 driven by the mammalian common promoter in dendritic cells International journal

    Naoto Ito, Fumiya Sakata, Masakazu Hachisu, Kazuki Nagata, Tomoka Ito, Kurumi Nomura, Masanori Nagaoka, Keito Inaba, Mutsuko Hara, Nobuhiro Nakano, Tadaaki Nakajima, Takuya Yashiro, Chiharu Nishiyama

    Allergy   77 ( 3 )   1054 - 1059   2021.11

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

    DOI： 10.1111/all.15184

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  • A 3D tissue model-on-a-chip for studying the effects of human senescent fibroblasts on blood vessels Reviewed International journal

    Joris Pauty, Shizuka Nakano, Ryo Usuba, Tadaaki Nakajima, Yoshikazu Johmura, Satotaka Omori, Naoya Sakamoto, Akihiko Kikuchi, Makoto Nakanishi, Yukiko T. Matsunaga

    Biomaterials Science   9 ( 1 )   199 - 211   2021.11

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Royal Society of Chemistry (RSC)  

    <p>Senescent cells modify their environment and cause tissue aging that leads to organ dysfunction. Developing strategies for healthy aging rises a need for <italic>in vitro</italic> models that enables to study senescence and senotherapeutics at a tissue level.</p>

    DOI： 10.1039/d0bm01297a

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  • New frontiers of developmental endocrinology opened by researchers connecting irreversible effects of sex hormones on developing organs Reviewed

    Taisen Iguchi, Tomomi Sato, Tadaaki Nakajima, Shinichi Miyagawa, Noboru Takasugi

    Differentiation   118   4 - 23   2021.3

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.diff.2020.10.003

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  • A clonal stem cell line established from a mouse mammary placode with ability to generate functional mammary glands. Reviewed

    Sakai Y, Miyake R, Shimizu T, Nakajima T, Sakakura T, Tomooka Y

    In vitro cellular & developmental biology. Animal   55 ( 10 )   861 - 871   2019.12

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  • Tetranins: new putative spider mite elicitors of host plant defense. Reviewed

    Iida J, Desaki Y, Hata K, Uemura T, Yasuno A, Islam M, Maffei ME, Ozawa R, Nakajima T, Galis I, Arimura GI

    The New phytologist   224 ( 2 )   875 - 885   2019.10

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

    DOI： 10.1111/nph.15813

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  • Design of a surface-functionalized power-free microchip for extracellular vesicle detection utilizing UV grafting Reviewed

    Ryo Ishihara, Asuka Katagiri, Tadaaki Nakajima, Ryo Matsui, Shuuhei Komatsu, Kazuo Hosokawa, Mizuo Maeda, Yasuhiro Tomooka, Akihiko Kikuchi

    Reactive and Functional Polymers   142   183 - 188   2019.6

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    Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.reactfunctpolym.2019.06.017

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  • Phenotypic analysis of endothelial cell function by using three-dimensional microvessel model Invited Reviewed

    Tadaaki NAKAJIMA, Yukiko T. MATSUNAGA

    Japanese Journal of Thrombosis and Hemostasis   30 ( 3 )   512 - 520   2019

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    Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society on Thrombosis and Hemostasis  

    DOI： 10.2491/jjsth.30.512

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  • Stratification of mouse vaginal epithelium. 1. Development of three-dimensional models in vitro with clonal cell lines. Reviewed

    Ogawa-Tominaga M, Umezu T, Nakajima T, Tomooka Y

    Biology of reproduction   99 ( 4 )   718 - 726   2018.10

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  • Stratification of mouse vaginal epithelium 2. Identification of factors inducing stratification. Reviewed

    Takashina R, Nakajima T, Umezu T, Komatsu K, Banba T, Asada T, Ohse K, Murakami Y, Tomooka Y

    Biology of reproduction   99 ( 4 )   727 - 734   2018.10

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  • Rapid and Easy Extracellular Vesicle Detection on a Surface-Functionalized Power-Free Microchip toward Point-of-Care Diagnostics Reviewed

    Ryo Ishihara, Tadaaki Nakajima, Yoshitaka Uchino, Asuka Katagiri, Kazuo Hosokawa, Mizuo Maeda, Yasuhiro Tomooka, Akihiko Kikuchi

    ACS Omega   2 ( 10 )   6703 - 6707   2017.10

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

    DOI： 10.1021/acsomega.7b01147

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  • Accumulation of immunoglobulin G against Dermatophagoides farinae tropomyosin in dorsal root ganglia of NC/Nga mice with atopic dermatitis-like symptoms Reviewed

    Ayaka Otsu, Hiroaki Kawasaki, Mitsutoshi Tominaga, Ayako Shigenaga, Hironori Matsuda, Nobuaki Takahashi, Tadaaki Nakajima, Hisashi Naito, Takeshi Baba, Hideoki Ogawa, Yasuhiro Tomooka, Fumiyuki Yamakura, Kenji Takamori

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   485 ( 4 )   707 - 712   2017.4

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    DOI： 10.1016/j.bbrc.2017.02.109

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  • Sex Reversal and Analyses of Possible Involvement of Sex Steroids in Scallop Gonadal Development in Newly Established Organ-Culture Systems Reviewed

    Ayano Otani, Tadaaki Nakajima, Tomomi Okumura, Shiro Fujii, Yasuhiro Tomooka

    ZOOLOGICAL SCIENCE   34 ( 2 )   86 - 92   2017.4

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    DOI： 10.2108/zs160070

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  • Role of extracellular vesicles in the interaction between epithelial and mesenchymal cells during oviductal ciliogenesis Reviewed

    Shota Nakano, Shohei Yamamoto, Atsumasa Okada, Tadaaki Nakajima, Mamiko Sato, Tomoko Takagi, Yasuhiro Tomooka

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   483 ( 1 )   245 - 251   2017.1

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    DOI： 10.1016/j.bbrc.2016.12.158

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  • Hedgehog signaling plays roles in epithelial cell proliferation in neonatal mouse uterus and vagina Reviewed

    Tadaaki Nakajima, Taisen Iguchi, Tomomi Sato

    CELL AND TISSUE RESEARCH   348 ( 1 )   239 - 247   2012.4

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    DOI： 10.1007/s00441-012-1350-7

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  • The role of fibroblast growth factors on the differentiation of vaginal epithelium of neonatal mice Reviewed

    Tadaaki Nakajima, Shinji Hayashi, Taisen Iguchi, Tomomi Sato

    DIFFERENTIATION   82 ( 1 )   28 - 37   2011.7

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    DOI： 10.1016/j.diff.2011.03.005

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  • Involvement of activin signaling in abnormalities of mouse vagina exposed neonatally to diethylstilbestrol Reviewed

    Tadaaki Nakajima, Taisen Iguchi, Tomomi Sato

    CELL AND TISSUE RESEARCH   344 ( 3 )   527 - 538   2011.6

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    DOI： 10.1007/s00441-011-1161-2

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  • Effects of Diethylstilbestrol on Programmed Oocyte Death and Induction of Polyovular Follicles in Neonatal Mouse Ovaries Reviewed

    Hannah Kim, Tadaaki Nakajima, Shinji Hayashi, Pierre Chambon, Hajime Watanabe, Taisen Iguchi, Tomomi Sato

    BIOLOGY OF REPRODUCTION   81 ( 5 )   1002 - 1009   2009.11

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    DOI： 10.1095/biolreprod.108.070599

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Books

  • Genomic and Epigenomic Biomarkers of Toxicology and Disease

    Tadaaki Nakajima, Tomomi Sato, Taisen Iguchi（ Role： Joint authorGenetic, Epigenetic, and Anatomical Factors in Agenesis and Development of Female Reproductive Tract）

    Wiley Professional, Reference & Trade  2022.4 

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  • Surface-functionalised power-free microchip

    Tadaaki Nakajima（ Role： Joint author）

    Impact  2019.3 

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  • 早期発見・予防に向けた次世代がん検査技術の最前線

    石原量, 中島忠章（ Role： Contributor第4編 デバイス開発および臨床研究，17章 がん診断のための細胞外ベシクル捕捉・破砕用マイクロチップの開発）

    シーエムシー出版  2019.2 

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  • 月刊 理大科学フォーラム

    中島忠章（ Role： Joint authorホタテの株細胞樹立を目指して）

    2018.6 

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  • Role of extracellular vesicles in the interaction between epithelial and mesenchymal cells during oviductal ciliogenesis

    Tadaaki Nakajima（ Role： Sole author）

    Biomedical Advances  2017.2 

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MISC

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Presentations

  • Visualization of vascular dynamics and phenotypic analysis by using three-dimensional microvessel model Invited

    Tadaaki Nakajima

    2019.12 

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  • Visualization of vascular dynamics using artificial microvessel model Invited International conference

    Tadaaki Nakajima

    Neuro2019  2019.7 

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    Language：English   Presentation type：Oral presentation (invited, special)  

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  • 周囲環境が誘導する雌性生殖器の形態形成機構 Invited

    中島忠章

    第８８回 生体制御学セミナー  2024.10 

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    Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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  • 三次元ヒト腸管モデルを用いた、管状領域制限が上皮形態形成に与える影響の解析

    中島忠章, 佐々木克典, 山森明弘, 櫻井研吾, 宮田かおり, 渡辺知幸, 松永行子

    日本動物学会 第91 回大会 

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    Event date： 2020.9

    Presentation type：Oral presentation (general)  

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  • 卵管間質の運命決定におけるTGFβシグナルの役割

    中島忠章, 山中里紗, 友岡康弘, 佐藤友美, 河野郷通, 松永行子

    日本動物学会 第89 回大会  2018.9 

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  • クローン性株細胞を用いた膣組織再構築系の開発

    上妻雅, 安富諒, 中島忠章, 大谷亨, 友岡康弘

    第39回日本バイオマテリアル学会大会  2017.11 

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  • Mechanisms of fate determination in mouse Müllerian ductal mesenchyme International conference

    Nakajima T, Yamanaka R, Sato T, Kohno S, Tomooka Y

    50th Annual Meeting of the Society for the Study of Reproduction  2017.7 

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  • Induction of direct differentiation into ameloblast by tooth germ mesenchyme International conference

    Konno K, Nakaijma T, Tomooka Y

    the 22nd International Congress of Zoolog  2016.11 

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  • Extracellular vesicle detection on a surface-functionalized power-free microchip toward point-of-care cancer diagnosis International conference

    Ishihara R, Nakajima T, Uchino Y, Tanabe K, Hosokawa K, Maeda M, Tomooka Y, Kikuchi A

    Liquid Biopsies and Minimally-Invasive Diagnostics 2016  2016.9 

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  • An attempt to establish culture system to identify mesenchymal factors determining the fate of Müllerian duct epithelial cells to uterine epithelial cells International conference

    Harada K, Tobita T, Nakaijma T, Tomooka Y

    the 22nd International Congress of Zoology  2016.11 

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  • An attempt to identify mesenchymal factors determining the fate of Müllerian duct epithelial cells to vaginal epithelial cells International conference

    Kozuma M, Sibusawa A, Nakajima T, Tomooka Y

    the 22nd International Congress of Zoology  2016.11 

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  • Generation of Müllerian ductal cells from mouse iPS cells by an analysis of development of Müllerian ducts International conference

    Ishii C, Nakajima T, Imai A Tomooka Y

    the 22nd International Congress of Zoology  2016.11 

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  • Monitoring induction of Wolffian ductal epithelial and mesenchymal cells from mouse iPS cells International conference

    Imai A, Nakajima T, Ishii C, Tomooka Y

    the 22nd International Congress of Zoology  2016.11 

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  • The role of fibroblast growth factor (FGF) 9, FGF10 and sonic hedgehog on the cell proliferation and differentiation of vaginal epithelium of neonatal mice International conference

    Nakajima T, Iguchi T, Sato T

    14th International Congress of Endocrinology  2010.3 

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  • 新生仔期エストロゲン受容体 (ER) βの子宮上皮細胞増殖抑制への関与

    中島忠章, 井口泰泉, 佐藤友美

    第14回日本生殖内分泌学会学術集会  2009.11 

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  • 新生仔期マウスの膣上皮細胞におけるFGFとHHの役割

    中島忠章, 井口泰泉, 佐藤友美

    日本動物学会 第80回大会  2009.9 

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  • レチノイン酸シグナルによる子宮間質の運命決定

    中島忠章, 佐藤友美, 友岡康弘

    日本動物学会 第84回大会  2013.9 

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  • 胎仔期から成熟期にかけての子宮と膣の分化におけるレチノイン酸シグナルの役割

    中島忠章, 井口泰泉, 佐藤友美

    日本動物学会 第83回大会  2012.9 

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  • 新生仔期マウスの子宮分化に働く因子の探索

    中島忠章, 井口泰泉, 佐藤友美

    日本動物学会 82回大会  2011.9 

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  • マウス膣上皮細胞増殖に促進的に働くSHHの作用

    中島忠章, 井口泰泉, 佐藤友美

    日本動物学会 第81回大会  2010.9 

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  • 新生仔期マウスの子宮と膣に対するDiethylstilbestrol (DES) とInhibinの影響

    中島忠章, 佐藤友美

    日本動物学会関東支部 第61回大会  2009.3 

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  • 新生仔期マウスの子宮と膣で発現する因子の解析

    中島忠章, 井口泰泉, 佐藤友美

    日本動物学会 第79回大会  2008.9 

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  • 新生仔マウスの子宮と膣の増殖と分化におけるエストロゲン受容体 (ER) の役割

    中島忠章, 金翰那, 佐藤友美

    日本動物学会関東支部 第60回大会  2008.3 

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  • 新生仔マウスの子宮と膣におけるFGFとHHファミリーの発現と局在

    中島忠章, 林しん治, 井口泰泉, 佐藤友美

    日本動物学会 第78回大会  2007.9 

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  • 新生仔マウスの子宮と膣におけるFGF (fibroblast growth factors) とHH (hedgehog) ファミリーの発現

    中島忠章, 佐藤友美, 林しん治

    日本動物学会関東支部 第59回大会  2007.3 

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  • マウス子宮頸部内部構造 (fornix) 上皮における二分化能幹細胞の探索

    中島忠章, 佐藤友美

    日本動物学会 第95 回大会  2024.9 

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  • マウス雌性生殖腺附属器官の押込応力測定による物性の推定と模倣

    中島忠章, 佐藤友美

    第47回 日本比較内分泌学会大会  2023.11 

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  • 足場の硬さが制御する膣間質細胞由来の上皮運命決定因子の発現機構

    中島忠章, 上妻雅, 平沢朋子, 友岡康弘, 松永行子

    日本動物学会 第90 回大会  2019.9 

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  • ERβノックアウトマウスの加齢にともなう子宮の形態変化過程の解析

    中島忠章, 能勢咲希, 松田紀香, 鶴貝優梨花, 佐藤友美

    日本動物学会 第94 回大会  2023.9 

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  • ERβノックアウトマウスの加齢にともなう子宮構造の変化

    中島忠章, 荒川玲奈, 石井真実, 柘植愛里, 佐藤友美

    日本動物学会 第93 回大会  2022.9 

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  • 三次元マウス子宮モデルを用いた子宮内腔上皮と子宮腺発生機構の解明

    中島忠章, 佐藤友美

    日本動物学会 第92 回大会  2021.9 

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  • Simple inner-surface modification of a PDMS microchip by radiation-induced graft polymerization for extracellular vesicle detection toward point-of-care cancer diagnosis International conference

    Ishihara R, Nakajima T, Uchino Y, Tanabe K, Hosokawa K, Maeda M, Tomooka Y, Kikuchi A

    10th World Biomaterials Congress  2016.5 

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  • マウスiPS 細胞を用いたヴォルフ管, ミュラー管細胞の誘導

    中島忠章, 鶴山功大, 今井章寛, 石井千尋, 友岡康弘

    日本動物学会 第86 回大会  2015.9 

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  • マウスiPS 細胞を用いたヴォルフ管, ミュラー管細胞の誘導

    中島忠章, 山中里紗, 鶴山功大, 友岡康弘

    日本動物学会 第85 回大会  2014.9 

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Industrial property rights

  • 3次元腸組織モデルの作製方法

    中島忠章, 松永行子, 住友化学株式会社

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Research Projects

  • Feedback signaling mechanism between cells and scaffold in the epithelial development

    Grant number：21K06244  2021.4 - 2024.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

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    Grant amount：\4290000 （ Direct Cost: \3300000 、 Indirect Cost：\990000 ）

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  • 壁細胞が制御する血管恒常性解析モデルの確立

    2020.3 - 2021.3

    上原記念生命科学財団  研究奨励金 第４部門 

    中島忠章

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    Authorship：Principal investigator  Grant type：Competitive

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  • 管状構造と物理的因子が誘導する上皮立体構造形成機構の解明

    2019.4 - 2021.3

    日本学術振興会  若手研究 

    中島忠章

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    Authorship：Principal investigator  Grant type：Competitive

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  • 管状培養系を用いた物理的因子の制御による子宮腺形成の誘導

    Grant number：24K09517  2024.4 - 2027.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    中島 忠章

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    Authorship：Principal investigator 

    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

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  • The primordial follicle assembly and activation in the neonatal mouse ovary

    Grant number：23K27202  2023.4 - 2026.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Grant amount：\18850000 （ Direct Cost: \14500000 、 Indirect Cost：\4350000 ）

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  • 中枢神経系原発悪性リンパ腫と血管の三次元共培養モデルを用いた革新的治療薬開発のためのプラットフォーム構築

    2023.4 - 2024.3

    横浜市立大学  学術的研究推進事業「YCU未来共創プロジェクト」 

    中島忠章

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  • 多嚢胞性卵巣症候群モデルマウス卵巣における遺伝子発現変化の解析

    2021.8 - 2022.3

    公益財団法人横浜学術教育振興財団  研究助成 

    中島忠章

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  • 卵管間質の運命決定におけるTGFβシグナルの役割

    2018.8 - 2019.3

    公益財団法人横浜学術教育振興財団  研究助成 

    中島忠章

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    Authorship：Principal investigator  Grant type：Competitive

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  • がん診断のための細胞外ベシクル捕捉・破砕用マイクロチップ開発

    2016.4 - 2018.3

    日本学術振興会  挑戦的萌芽研究 

    石原量

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    Grant type：Competitive

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  • 子宮頸ガン早期診断のための細胞内核酸解析

    2016.4 - 2017.3

    東京理科大学  若手共同研究助成金 

    中島忠章

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    Authorship：Principal investigator  Grant type：Competitive

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  • 早期診断・疾患解析のための細胞外ベシクル解析用グラフト型マイクロチップの開発

    2015.4 - 2017.3

    東京理科大学  戦略研究課題助成金 

    石原量

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    Grant type：Competitive

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  • 雌性生殖器官原基の誘導因子の探索

    2013.4 - 2016.3

    日本学術振興会  基盤研究 (C) 

    友岡康弘

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    Grant type：Competitive

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  • 新生仔期マウスの子宮と膣上皮の分化メカニズムの解明

    Grant number：11J03897  2011.4 - 2012.3

    日本学術振興会  科学研究費助成事業  特別研究員奨励費

    中島 忠章

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    Grant amount：\1300000 （ Direct Cost: \1300000 ）

    膣形成不全患者に対して、膣口付近の上皮を伸長させる膣形成手術が行われているが、時間がかかり、その上皮が膣に近いのかもわかっていない,,横浜市立大学医学部産婦人科との共同研究により、再建された膣上皮の構造タンパク質とエストロゲン受容体の発現は、膣上皮に近かった,,このことから、再建された膣上皮は、膣に近いことが示された、,30日齢のマウスの膣を器官培養し、FGF2とE2を単独または共添加したところ、FGF2とE2の共添加時にのみ、膣上皮の細胞増殖が促進された。このことは、再建膣といった通常の膣よりも条件の悪い環境下においても、FGF2とE2の両方が存在することで、膣上皮の細胞増殖が促進される可能性があることを示唆している。
    子宮上皮の分化に働く新たな候補因子として、レチノイン酸(RA)を発見した,RAシグナルのmRNAとタンパク質発現を、胎生14.5日齢から成体におけるまで調べたところ、合成酵素の発現が子宮で常に高かった。RAが活性化している時期と場所を調べたところ、胎仔期のミュラー管の基部と中部の間質で活性化しており、尾部では活性化していないことがわかった。ミュラー管の基部,中部,尾部は、それぞれ卵管,子宮,膣になる領域である。器官培養したミュラー管尾部にRAを添加したところ、将来膣に分化する予定の上皮細胞が、子宮上皮細胞へと分化し、ミュラー管中部にRA受容体の阻害剤を添加すると、将来子宮に分化する予定の上皮細胞が、膣上皮細胞へと分化した。RAまたはRA受容体の阻害剤を添加して、宿主マウスの腎被膜下に1ヶ月間移植したところ、器官培養時に変化した上皮細胞の運命が、不可逆的であることがわかった。以上の結果より、子宮上皮の分化は胎仔期のRAシグナルによって誘導され、膣上皮の分化はRAシグナルがなくなることで誘導されることが考えられる。

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Teaching Experience

  • 生命科学と安全論

    Institution：東京理科大学

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  • 生物工学実験VI：組織発生工学

    Institution：東京理科大学

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  • 生物学概論実験Ｉ：生理学

    Institution：日本女子大学

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