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  1. Article ; Online: Inhibition of Histone Methyltransferase, Histone Deacetylase, and β-Catenin Synergistically Enhance the Cardiac Potential of Bone Marrow Cells

    Jinpu Yang / Keerat Kaur / John G. Edwards / Carol A. Eisenberg / Leonard M. Eisenberg

    Stem Cells International, Vol

    2017  Volume 2017

    Abstract: Previously, we reported that treatment with the G9a histone methyltransferase inhibitor BIX01294 causes bone marrow mesenchymal stem cells (MSCs) to exhibit a cardiocompetent phenotype, as indicated by the induction of the precardiac markers Mesp1 and ... ...

    Abstract Previously, we reported that treatment with the G9a histone methyltransferase inhibitor BIX01294 causes bone marrow mesenchymal stem cells (MSCs) to exhibit a cardiocompetent phenotype, as indicated by the induction of the precardiac markers Mesp1 and brachyury. Here, we report that combining the histone deacetylase inhibitor trichostatin A (TSA) with BIX01294 synergistically enhances MSC cardiogenesis. Although TSA by itself had no effect on cardiac gene expression, coaddition of TSA to MSC cultures enhanced BIX01294-induced levels of Mesp1 and brachyury expression 5.6- and 7.2-fold. Moreover, MSCs exposed to the cardiogenic stimulus Wnt11 generated 2.6- to 5.6-fold higher levels of the cardiomyocyte markers GATA4, Nkx2.5, and myocardin when pretreated with TSA in addition to BIX01294. MSC cultures also showed a corresponding increase in the prevalence of sarcomeric protein-positive cells when treated with these small molecule inhibitors. These results correlated with data showing synergism between (1) TSA and BIX01294 in promoting acetylation of lysine 27 on histone H3 and (2) BIX01294 and Wnt11 in decreasing β-catenin accumulation in MSCs. The implications of these findings are discussed in light of observations in the early embryo on the importance of β-catenin signaling and histone modifications for cardiomyocyte differentiation and heart development.
    Keywords Internal medicine ; RC31-1245
    Subject code 572
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Inhibition of G9a Histone Methyltransferase Converts Bone Marrow Mesenchymal Stem Cells to Cardiac Competent Progenitors

    Jinpu Yang / Keerat Kaur / Li Lin Ong / Carol A. Eisenberg / Leonard M. Eisenberg

    Stem Cells International, Vol

    2015  Volume 2015

    Keywords Medicine ; R ; Internal medicine ; RC31-1245
    Publishing date 2015-01-01T00:00:00Z
    Publisher Hindawi Publishing Corporation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Inhibition of G9a Histone Methyltransferase Converts Bone Marrow Mesenchymal Stem Cells to Cardiac Competent Progenitors

    Jinpu Yang / Keerat Kaur / Li Lin Ong / Carol A. Eisenberg / Leonard M. Eisenberg

    Stem Cells International, Vol

    2015  Volume 2015

    Abstract: The G9a histone methyltransferase inhibitor BIX01294 was examined for its ability to expand the cardiac capacity of bone marrow cells. Inhibition of G9a histone methyltransferase by gene specific knockdown or BIX01294 treatment was sufficient to induce ... ...

    Abstract The G9a histone methyltransferase inhibitor BIX01294 was examined for its ability to expand the cardiac capacity of bone marrow cells. Inhibition of G9a histone methyltransferase by gene specific knockdown or BIX01294 treatment was sufficient to induce expression of precardiac markers Mesp1 and brachyury in bone marrow cells. BIX01294 treatment also allowed bone marrow mesenchymal stem cells (MSCs) to express the cardiac transcription factors Nkx2.5, GATA4, and myocardin when subsequently exposed to the cardiogenic stimulating factor Wnt11. Incubation of BIX01294-treated MSCs with cardiac conditioned media provoked formation of phase bright cells that exhibited a morphology and molecular profile resembling similar cells that normally form from cultured atrial tissue. Subsequent aggregation and differentiation of BIX01294-induced, MSC-derived phase bright cells provoked their cardiomyogenesis. This latter outcome was indicated by their widespread expression of the primary sarcomeric proteins muscle α-actinin and titin. MSC-derived cultures that were not initially treated with BIX01294 exhibited neither a commensurate burst of phase bright cells nor stimulation of sarcomeric protein expression. Collectively, these data indicate that BIX01294 has utility as a pharmacological agent that could enhance the ability of an abundant and accessible stem cell population to regenerate new myocytes for cardiac repair.
    Keywords Internal medicine ; RC31-1245
    Subject code 616
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  4. Article ; Online: Evaluating the Role of Wnt Signal Transduction in Promoting the Development of the Heart

    Leonard M. Eisenberg / Carol A. Eisenberg

    The Scientific World Journal, Vol 7, Pp 161-

    2007  Volume 176

    Abstract: Wnts are a family of secreted signaling proteins that are encoded by 19 distinct genes in the vertebrate genome. These molecules initiate several signal transduction pathways: the canonical Wnt, Wnt/Ca2+, and Wnt/planar cell polarity pathways. Wnt ... ...

    Abstract Wnts are a family of secreted signaling proteins that are encoded by 19 distinct genes in the vertebrate genome. These molecules initiate several signal transduction pathways: the canonical Wnt, Wnt/Ca2+, and Wnt/planar cell polarity pathways. Wnt proteins have major impact on embryonic development, tumor progression, and stem cell differentiation. Wnt signal transduction also influences the formation of the heart, yet many issues concerning the involvement of Wnt regulation in initiating cardiac development remain unresolved. In this review, we will examine the published record to discern (a) what has been shown by experimental studies on the participation of Wnt signaling in cardiogenesis, and (b) what are the important questions that need to be addressed to understand the importance and function of Wnt signal transduction in facilitating the development of the heart.
    Keywords Technology ; T ; Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2007-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  5. Article ; Online: Mesenchymal stem cell-cardiomyocyte interactions under defined contact modes on laser-patterned biochips.

    Zhen Ma / Huaxiao Yang / Honghai Liu / Meifeng Xu / Raymond B Runyan / Carol A Eisenberg / Roger R Markwald / Thomas K Borg / Bruce Z Gao

    PLoS ONE, Vol 8, Iss 2, p e

    2013  Volume 56554

    Abstract: Understanding how stem cells interact with cardiomyocytes is crucial for cell-based therapies to restore the cardiomyocyte loss that occurs during myocardial infarction and other cardiac diseases. It has been thought that functional myocardial repair and ...

    Abstract Understanding how stem cells interact with cardiomyocytes is crucial for cell-based therapies to restore the cardiomyocyte loss that occurs during myocardial infarction and other cardiac diseases. It has been thought that functional myocardial repair and regeneration could be regulated by stem cell-cardiomyocyte contact. However, because various contact modes (junction formation, cell fusion, partial cell fusion, and tunneling nanotube formation) occur randomly in a conventional coculture system, the particular regulation corresponding to a specific contact mode could not be analyzed. In this study, we used laser-patterned biochips to define cell-cell contact modes for systematic study of contact-mediated cellular interactions at the single-cell level. The results showed that the biochip design allows defined stem cell-cardiomyocyte contact-mode formation, which can be used to determine specific cellular interactions, including electrical coupling, mechanical coupling, and mitochondria transfer. The biochips will help us gain knowledge of contact-mediated interactions between stem cells and cardiomyocytes, which are fundamental for formulating a strategy to achieve stem cell-based cardiac tissue regeneration.
    Keywords Medicine ; R ; Science ; Q
    Subject code 571
    Language English
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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