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  1. Article: An improved clonogenic culture method for thymic epithelial cells

    Sekai, Miho / Jianwei Wang / Nagahiro Minato / Yoko Hamazaki

    Journal of immunological methods. 2019 Feb. 05,

    2019  

    Abstract: A clonogenic assay system for thymic epithelial cells (TECs) is of crucial importance for identifying thymic epithelial stem and/or progenitor cells, evaluating their activities, and understanding the mechanisms of thymic involution. However, current ... ...

    Abstract A clonogenic assay system for thymic epithelial cells (TECs) is of crucial importance for identifying thymic epithelial stem and/or progenitor cells, evaluating their activities, and understanding the mechanisms of thymic involution. However, current systems are not sufficiently sensitive at detecting and quantifying TEC colonies from the adult thymus. Here, we optimized the culture condition to detect visible colonies from adult TECs by modifying our previous culture methods. Epidermal growth factor and leukemia inhibitory factor significantly enhanced the colony-forming efficiency of total TECs from embryo as well as adult mice when added 3 days after plating. Importantly, characteristics of the TEC colonies formed by the improved condition were almost equivalent to those by the original culture condition with respect to self-renewal and the expression of cell surface markers and intracellular keratins. Furthermore, the colonies derived from total TECs showed immature phenotypes and generated both mature cortical TECs and medullary TECs upon implantation in vivo. These data indicate a more sensitive clonogenic assay system for TECs was established and suggest the improved culture condition supports the colony formation of stem/progenitor cells for cTECs, mTECs and/or bipotent TECs.
    Keywords adults ; embryo (animal) ; epidermal growth factor ; epithelial cells ; epithelium ; leukemia inhibitory factor ; mice ; phenotype ; stem cells ; thymus gland
    Language English
    Dates of publication 2019-0205
    Size p. .
    Publishing place Elsevier B.V.
    Document type Article
    Note Pre-press version
    ZDB-ID 120142-6
    ISSN 1872-7905 ; 0022-1759
    ISSN (online) 1872-7905
    ISSN 0022-1759
    DOI 10.1016/j.jim.2019.02.003
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Cologne/Königswinter

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  2. Book ; Online: Innovative Medicine

    Nagahiro Minato / Shinji Uemoto / Kazuwa Nakao

    Basic Research and Development

    2015  

    Abstract: This book is devoted to innovative medicine, comprising the proceedings of the Uehara Memorial Foundation Symposium 2014. It remains extremely rare for the findings of basic research to be developed into clinical applications, and it takes a long time ... ...

    Abstract This book is devoted to innovative medicine, comprising the proceedings of the Uehara Memorial Foundation Symposium 2014. It remains extremely rare for the findings of basic research to be developed into clinical applications, and it takes a long time for the process to be achieved. The task of advancing the development of basic research into clinical reality lies with translational science, yet the field seems to struggle to find a way to move forward. To create innovative medical technology, many steps need to be taken: development and analysis of optimal animal models of human diseases, elucidation of genomic and epidemiological data, and establishment of “proof of concept”. There is also considerable demand for progress in drug research, new surgical procedures, and new clinical devices and equipment. While the original research target may be rare diseases, it is also important to apply those findings more broadly to common diseases. The book covers a wide range of topics and is organized into three complementary parts. The first part is basic research for innovative medicine, the second is translational research for innovative medicine, and the third is new technology for innovative medicine. This book helps to understand innovative medicine and to make progress in its realization.
    Keywords molecular medicine ; immunology ; cell biology
    Language English
    Publisher Springer Nature
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Book ; Online: Innovative Medicine

    Kazuwa Nakao / Nagahiro Minato / Shinji Uemoto

    Basic Research and Development

    2015  

    Abstract: molecular medicine; immunology; cell ... ...

    Abstract molecular medicine; immunology; cell biology
    Keywords molecular medicine ; immunology ; cell biology ; M
    Language English
    Publisher Springer
    Publishing country nl
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Sipa1 deficiency unleashes a host-immune mechanism eradicating chronic myelogenous leukemia-initiating cells

    Yan Xu / Satoshi Ikeda / Kentaro Sumida / Ryusuke Yamamoto / Hiroki Tanaka / Nagahiro Minato

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 14

    Abstract: Chronic myelogenous leukemia (CML)-initiating cells are resistant to kinase inhibitors. Here the authors show that deficiency of the Rap1 GTPase-activating protein Sipa1 in the tumor microenvironment releases an immune response that eradicates CML- ... ...

    Abstract Chronic myelogenous leukemia (CML)-initiating cells are resistant to kinase inhibitors. Here the authors show that deficiency of the Rap1 GTPase-activating protein Sipa1 in the tumor microenvironment releases an immune response that eradicates CML-initiating cells via interplay between stromal and T cells.
    Keywords Science ; Q
    Language English
    Publishing date 2018-03-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Sipa1 deficiency unleashes a host-immune mechanism eradicating chronic myelogenous leukemia-initiating cells

    Yan Xu / Satoshi Ikeda / Kentaro Sumida / Ryusuke Yamamoto / Hiroki Tanaka / Nagahiro Minato

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 14

    Abstract: Chronic myelogenous leukemia (CML)-initiating cells are resistant to kinase inhibitors. Here the authors show that deficiency of the Rap1 GTPase-activating protein Sipa1 in the tumor microenvironment releases an immune response that eradicates CML- ... ...

    Abstract Chronic myelogenous leukemia (CML)-initiating cells are resistant to kinase inhibitors. Here the authors show that deficiency of the Rap1 GTPase-activating protein Sipa1 in the tumor microenvironment releases an immune response that eradicates CML-initiating cells via interplay between stromal and T cells.
    Keywords Science ; Q
    Language English
    Publishing date 2018-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Enteroendocrine cells are specifically marked by cell surface expression of claudin-4 in mouse small intestine.

    Takahiro Nagatake / Harumi Fujita / Nagahiro Minato / Yoko Hamazaki

    PLoS ONE, Vol 9, Iss 6, p e

    2014  Volume 90638

    Abstract: Enteroendocrine cells are solitary epithelial cells scattered throughout the gastrointestinal tract and produce various types of hormones, constituting one of the largest endocrine systems in the body. The study of these rare epithelial cells has been ... ...

    Abstract Enteroendocrine cells are solitary epithelial cells scattered throughout the gastrointestinal tract and produce various types of hormones, constituting one of the largest endocrine systems in the body. The study of these rare epithelial cells has been hampered by the difficulty in isolating them because of the lack of specific cell surface markers. Here, we report that enteroendocrine cells selectively express a tight junction membrane protein, claudin-4 (Cld4), and are efficiently isolated with the use of an antibody specific for the Cld4 extracellular domain and flow cytometry. Sorted Cld4+ epithelial cells in the small intestine exclusively expressed a chromogranin A gene (Chga) and other enteroendocrine cell-related genes (Ffar1, Ffar4, Gpr119), and the population was divided into two subpopulations based on the activity of binding to Ulex europaeus agglutinin-1 (UEA-1). A Cld4+UEA-1- cell population almost exclusively expressed glucose-dependent insulinotropic polypeptide gene (Gip), thus representing K cells, whereas a Cld4+UEA-1+ cell population expressed other gut hormone genes, including glucagon-like peptide 1 (Gcg), pancreatic polypeptide-like peptide with N-terminal tyrosine amide (Pyy), cholecystokinin (Cck), secretin (Sct), and tryptophan hydroxylase 1 (Tph1). In addition, we found that orally administered luminal antigens were taken up by the solitary Cld4+ cells in the small intestinal villi, raising the possibility that enteroendocrine cells might also play a role in initiation of mucosal immunity. Our results provide a useful tool for the cellular and functional characterization of enteroendocrine cells.
    Keywords Medicine ; R ; Science ; Q
    Subject code 571
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Modification of Gene Expression, Proliferation, and Function of OP9 Stroma Cells by Bcr-Abl-Expressing Leukemia Cells.

    Emmanuelle Supper / Suhail Tahir / Takahiko Imai / Joe Inoue / Nagahiro Minato

    PLoS ONE, Vol 10, Iss 7, p e

    2015  Volume 0134026

    Abstract: Expression of the Bcr-Abl fusion gene in hematopoietic progenitor cells (HPCs) results in the development of chronic myelogenous leukemia (CML), for which hematopoietic microenvironment plays an important role. We investigated the specific effects of an ... ...

    Abstract Expression of the Bcr-Abl fusion gene in hematopoietic progenitor cells (HPCs) results in the development of chronic myelogenous leukemia (CML), for which hematopoietic microenvironment plays an important role. We investigated the specific effects of an HPC line transduced with Bcr-Abl, KOBA, on BM-derived OP9 stroma cells. DNA microarray analysis revealed that OP9 cells co-cultured with KOBA cells (OP9/L) show diverse changes in the gene expression. OP9/L cells showed significant down-regulation of Cdkn genes and up-regulation of Icam1, leading to the increased proliferation capacity of OP9 cells and enhanced transmigration of leukemia cells through them. The effects were attributed to direct Notch activation of OP9 cells by KOBA cells. OP9/L cells also showed a markedly altered cytokine gene expression pattern, including a robust increase in a variety of proinflammatory genes and a decrease in hematopoietic cytokines such as Cxcl12, Scf, and Angpt1. Consequently, OP9/L cells promoted the proliferation of KOBA cells more efficiently than parental OP9 cells, whereas the activity supporting normal myelopoiesis was attenuated. In mice bearing KOBA leukemia, the characteristic genetic changes observed in OP9/L cells were reflected differentially in the endothelial cells (ECs) and mesenchymal stroma cells (MCs) of the BM. The ECs were markedly increased with Notch-target gene activation and decreased Cdkn expression, whereas the MCs showed a marked increase in proinflammatory gene expression and a profound decrease in hematopoietic genes. Human CML cell lines also induced essentially similar genetic changes in OP9 cells. Our results suggest that CML cells remodel the hematopoietic microenvironment by changing the gene expression patterns differentially in ECs and MCs of BM.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Innate CD8αα+ cells promote ILC1-like intraepithelial lymphocyte homeostasis and intestinal inflammation.

    Ali Nazmi / Kristen L Hoek / Michael J Greer / Maria B Piazuelo / Nagahiro Minato / Danyvid Olivares-Villagómez

    PLoS ONE, Vol 14, Iss 7, p e

    2019  Volume 0215883

    Abstract: Innate CD8αα+ cells, also referred to as iCD8α cells, are TCR-negative intraepithelial lymphocytes (IEL) possessing cytokine and chemokine profiles and functions related to innate immune cells. iCD8α cells constitute an important source of osteopontin in ...

    Abstract Innate CD8αα+ cells, also referred to as iCD8α cells, are TCR-negative intraepithelial lymphocytes (IEL) possessing cytokine and chemokine profiles and functions related to innate immune cells. iCD8α cells constitute an important source of osteopontin in the intestinal epithelium. Osteopontin is a pleiotropic cytokine with diverse roles in bone and tissue remodeling, but also has relevant functions in the homeostasis of immune cells. In this report, we present evidence for the role of iCD8α cells in the homeostasis of TCR-negative NKp46+NK1.1+ IEL (ILC1-like). We also show that the effect of iCD8α cells on ILC1-like IEL is enhanced in vitro by osteopontin. We show that in the absence of iCD8α cells, the number of NKp46+NK1.1+ IEL is significantly reduced. These ILC1-like cells are involved in intestinal pathogenesis in the anti-CD40 mouse model of intestinal inflammation. Reduced iCD8α cell numbers results in a milder form of intestinal inflammation in this disease model, whereas treatment with osteopontin increases disease severity. Collectively, our results suggest that iCD8α cells promote survival of NKp46+NK1.1+ IEL, which significantly impacts the development of intestinal inflammation.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: SIPA1 enhances SMAD2/3 expression to maintain stem cell features in breast cancer cells

    Ning Wang / Jun Weng / Jing Xia / Yangjin Zhu / Qiongrong Chen / Die Hu / Xue Zhang / Rui Sun / Jueping Feng / Nagahiro Minato / Yiping Gong / Li Su

    Stem Cell Research, Vol 49, Iss , Pp 102099- (2020)

    2020  

    Abstract: SIPA1, a GTPase activating protein that negatively regulates Ras-related protein (Rap), is a potential modulator of tumor metastasis and recurrence. In this study, we first showed that SIPA1 facilitated the stemness features of breast cancer cells, such ... ...

    Abstract SIPA1, a GTPase activating protein that negatively regulates Ras-related protein (Rap), is a potential modulator of tumor metastasis and recurrence. In this study, we first showed that SIPA1 facilitated the stemness features of breast cancer cells, such as of tumorsphere formation capability and the expression of stemness marker CD44. In addition, SIPA1 promoted the expression of four stemness-associated transcription factors through increasing the expression of SMAD2 and SMAD3 in vitro and in vivo. The stemness features were abolished by blocking the phosphorylation of SMAD3 with its specific inhibitor SIS3. Furthermore, SIPA1 decreased the breast cancer cell sensitivity to chemotherapy drugs. This effect was, however, competitively reversed by blocking the SMAD3 phosphorylation by SIS3 treatment in breast cancer cells. Taken together, SIPA1 promotes and sustains the stemness of breast cancer cells and their resistance to chemotherapy by increasing the expression of SMAD2 and SMAD3, and blocking SMAD3 phosphorylation could suppress the cancer cell stemness and increase the sensitivity to chemotherapy in breast cancer cells expressing a high level of SIPA1.
    Keywords Breast cancer ; Cancer stem cell ; SIPA1 ; SMADs ; CD44 ; Biology (General) ; QH301-705.5
    Subject code 610 ; 616
    Language English
    Publishing date 2020-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: CD153/CD30 signaling promotes age-dependent tertiary lymphoid tissue expansion and kidney injury

    Yuki Sato / Akiko Oguchi / Yuji Fukushima / Kyoko Masuda / Naoya Toriu / Keisuke Taniguchi / Takahisa Yoshikawa / Xiaotong Cui / Makiko Kondo / Takeshi Hosoi / Shota Komidori / Yoko Shimizu / Harumi Fujita / Li Jiang / Yingyi Kong / Takashi Yamanashi / Jun Seita / Takuya Yamamoto / Shinya Toyokuni /
    Yoko Hamazaki / Masakazu Hattori / Yasunobu Yoshikai / Peter Boor / Jürgen Floege / Hiroshi Kawamoto / Yasuhiro Murakawa / Nagahiro Minato / Motoko Yanagita

    The Journal of Clinical Investigation, Vol 132, Iss

    2022  Volume 2

    Abstract: Tertiary lymphoid tissues (TLTs) facilitate local T and B cell interactions in chronically inflamed organs. However, the cells and molecular pathways that govern TLT formation are poorly defined. Here, we identified TNF superfamily CD153/CD30 signaling ... ...

    Abstract Tertiary lymphoid tissues (TLTs) facilitate local T and B cell interactions in chronically inflamed organs. However, the cells and molecular pathways that govern TLT formation are poorly defined. Here, we identified TNF superfamily CD153/CD30 signaling between 2 unique age-dependent lymphocyte subpopulations, CD153+PD-1+CD4+ senescence-associated T (SAT) cells and CD30+T-bet+ age-associated B cells (ABCs), as a driver for TLT expansion. SAT cells, which produced ABC-inducing factors IL-21 and IFN-γ, and ABCs progressively accumulated within TLTs in aged kidneys after injury. Notably, in kidney injury models, CD153 or CD30 deficiency impaired functional SAT cell induction, which resulted in reduced ABC numbers and attenuated TLT formation with improved inflammation, fibrosis, and renal function. Attenuated TLT formation after transplantation of CD153-deficient bone marrow further supported the importance of CD153 in immune cells. Clonal analysis revealed that SAT cells and ABCs in the kidneys arose from both local differentiation and recruitment from the spleen. In the synovium of aged rheumatoid arthritis patients, T peripheral helper/T follicular helper cells and ABCs also expressed CD153 and CD30, respectively. Together, our data reveal a previously unappreciated function of CD153/CD30 signaling in TLT formation and propose targeting the CD153/CD30 signaling pathway as a therapeutic target for slowing kidney disease progression.
    Keywords Inflammation ; Nephrology ; Medicine ; R
    Subject code 570
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher American Society for Clinical Investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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