Microenvironment

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Hyun Goo Woo - One of the best experts on this subject based on the ideXlab platform.

  • abstract 4283 cross species hybridization of microarrays for studying tumor transcriptome of brain metastasis
    Cancer Research, 2012
    Co-Authors: Eun Sung Park, Sun Jin Kim, Seung Wook Kim, Se Lyun Yoon, Sun Hee Leem, Sang Bae Kim, Soo Mi Kim, Yun Yong Park, Jae Ho Cheong, Hyun Goo Woo
    Abstract:

    Although the importance of the cellular Microenvironment (soil) during invasion and metastasis of cancer cells (seed) has been well-recognized, technical challenges have limited the ability to assess the influence of the Microenvironment on cancer cells at the molecular level. Here, we show that an experimental strategy, competitive cross-species hybridization of microarray experiments, can characterize the influence of different Microenvironments on cancer cells by independently extracting gene expression data of cancer and host cells when human cancer cells were xenografted into different organ sites of immunocompromised mice. Surprisingly, the analysis of gene expression data showed that the brain Microenvironment induces complete reprogramming of metastasized cancer cells, resulting in a gain of neuronal cell characteristics and mimicking neurogenesis during development. We also show that epigenetic changes coincide with transcriptional reprogramming in cancer cells. These observations provide proof of principle for competitive cross-species hybridization of microarray experiments to characterize the effect of the Microenvironment on tumor cell behavior Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4283. doi:1538-7445.AM2012-4283

  • cross species hybridization of microarrays for studying tumor transcriptome of brain metastasis
    Proceedings of the National Academy of Sciences of the United States of America, 2011
    Co-Authors: Eun Sung Park, Sun Jin Kim, Seung Wook Kim, Se Lyun Yoon, Sun Hee Leem, Sang Bae Kim, Soo Mi Kim, Yun Yong Park, Jae Ho Cheong, Hyun Goo Woo
    Abstract:

    Although the importance of the cellular Microenvironment (soil) during invasion and metastasis of cancer cells (seed) has been well-recognized, technical challenges have limited the ability to assess the influence of the Microenvironment on cancer cells at the molecular level. Here, we show that an experimental strategy, competitive cross-species hybridization of microarray experiments, can characterize the influence of different Microenvironments on cancer cells by independently extracting gene expression data of cancer and host cells when human cancer cells were xenografted into different organ sites of immunocompromised mice. Surprisingly, the analysis of gene expression data showed that the brain Microenvironment induces complete reprogramming of metastasized cancer cells, resulting in a gain of neuronal cell characteristics and mimicking neurogenesis during development. We also show that epigenetic changes coincide with transcriptional reprogramming in cancer cells. These observations provide proof of principle for competitive cross-species hybridization of microarray experiments to characterize the effect of the Microenvironment on tumor cell behavior.

Brendan A C Harley - One of the best experts on this subject based on the ideXlab platform.

  • Challenges and Opportunities to Harnessing the (Hematopoietic) Stem Cell Niche
    Stem cell reports, 2016
    Co-Authors: Ji Sun Choi, Brendan A C Harley
    Abstract:

    In our body, stem cells reside in a Microenvironment termed the niche. While the exact composition and, therefore, the level of complexity of a stem cell niche can vary significantly tissue-to-tissue, the stem cell niche Microenvironment is dynamic, typically containing spatial and temporal variations in both cellular, extracellular matrix, and biomolecular components. This complex flow of secreted or bound biomolecules, cytokines, extracellular matrix components, and cellular constituents all contributes to the regulation of stem cell fate specification events, making engineering approaches at the nanoscale and microscale of particular interest for creating an artificial niche environment in vitro. Recent advances in fabrication approaches have enabled biomedical researchers to capture and recreate the complexity of stem cell niche Microenvironments in vitro. Such engineered platforms show promise as a means to enhance our understanding of the mechanisms underlying niche-mediated stem cell regulation as well as offer opportunities to precisely control stem cell expansion and differentiation events for clinical applications. While these principles generally apply to all adult stem cells and niches, in this review, we focus on recent developments in engineering synthetic niche Microenvironments for one of the best-characterized stem cell populations, hematopoietic stem cells (HSCs). Specifically, we highlight recent advances in platforms designed to facilitate the extrinsic control of HSC fate decisions.

  • Challenges and Opportunities to Harnessing the (Hematopoietic) Stem Cell Niche
    Current stem cell reports, 2016
    Co-Authors: Ji Sun Choi, Brendan A C Harley
    Abstract:

    In our body, stem cells reside in a Microenvironment termed the niche. While the exact composition and therefore the level of complexity of a stem cell niche can vary significantly tissue-to-tissue, the stem cell niche Microenvironment is dynamic, typically containing spatial and temporal variations in both cellular, extracellular matrix, and biomolecular components. This complex flow of secreted or bound biomolecules, cytokines, extracellular matrix components, and cellular constituents all contribute to the regulation of stem cell fate specification events, making engineering approaches at the nano- and micro-scale of particular interest for creating an artificial niche environment in vitro. Recent advances in fabrication approaches have enabled biomedical researchers to capture and recreate the complexity of stem cell niche Microenvironments in vitro. Such engineered platforms show promise as a means to enhance our understanding of the mechanisms underlying niche-mediated stem cell regulation as well as offer opportunities to precisely control stem cell expansion and differentiation events for clinical applications. While these principles generally apply to all adult stem cells and niches, in this review, we focus on recent developments in engineering synthetic niche Microenvironments for one of the best-characterized stem cell populations, hematopoietic stem cells (HSC). Specifically, we highlight recent advances in platforms designed to facilitate the extrinsic control of HSC fate decisions.

  • The combined influence of substrate elasticity and ligand density on the viability and biophysical properties of hematopoietic stem and progenitor cells.
    Biomaterials, 2012
    Co-Authors: Ji Sun Choi, Brendan A C Harley
    Abstract:

    Hematopoietic stem cells (HSCs) are adult stem cells with the capacity to give rise to all blood and immune cells in the body. HSCs are housed in a specialized Microenvironment known as the stem cell niche, which provides intrinsic and extrinsic signals to regulate HSC fate: quiescence, self-renewal, differentiation, mobilization, homing, and apoptosis. These niches provide a complex, three dimensional (3D) Microenvironment consisting of cells, the extracellular matrix (ECM), and ECM-bound or soluble biomolecules that provides cellular, structural, and molecular signals that regulate HSC fate decisions. In this study, we examined the decoupled effects of substrate elasticity, construct dimensionality, and ligand concentration on the biophysical properties of primary hematopoietic stem and progenitor cells (HSPCs) using homologous series of two and three dimensional Microenvironments. Microenvironments were chosen to span the range of biophysical environments presented physiologically within the bone marrow, ranging from soft marrow and adipose tissue ( 30 kPa). We additionally investigated the influence of collagen ligand density on HSPC biophysical parameters and compared these behaviors to those observed in HSPCs grown in culture on stiff glass substrates. This work suggests the potential for substrate stiffness and ligand density to directly affect the biophysical properties of primary hematopoietic stem and progenitor cells at the single cell level and that these parameters may be critical design criteria for the development of artificial HSC niches.

Jeffrey L Browning - One of the best experts on this subject based on the ideXlab platform.

  • lymphotoxin light lymphoid Microenvironments and autoimmune disease
    Nature Reviews Immunology, 2003
    Co-Authors: Jennifer L Gommerman, Jeffrey L Browning
    Abstract:

    Much of the efficiency of the immune system is attributed to the high degree of spatial and temporal organization in the secondary lymphoid organs. Signalling through the lymphotoxin (LT) pathway is a crucial element in the maintenance of this organized Microenvironment. The effect of altering lymphoid Microenvironments on immune responses remains relatively unexplored. Inhibitors of the LT and LIGHT pathways have been shown to reduce disease in a wide range of autoimmune models. This approach has provided a tool to probe the effect of manipulation of the Microenvironment on both normal and pathological immune responses.

  • Lymphotoxin/LIGHT, lymphoid Microenvironments and autoimmune disease
    Nature Reviews Immunology, 2003
    Co-Authors: Jennifer L Gommerman, Jeffrey L Browning
    Abstract:

    To facilitate the encounter between lymphocytes and pathogens, the immune system has developed highly structured environments in the lymph nodes and marginal zones of the spleen. Signalling through the lymphotoxin (LT)/LIGHT pathways are crucial for the maintenance of these environments. These interactions are complex and, although the role of LT in the spleen has been well described, our understanding of its role in lymph nodes and mucosal sites is preliminary. Analysis of the effects of inhibitors of the LT/LIGHT system, which have been shown to reduce disease in many autoimmune models, can help us to understand the influence of lymphoid Microenvironments on immune responses. Here, our understanding of the role of LT/LIGHT signalling in the regulation of lymphoid Microenvironments in the spleen, lymph nodes and mucosal system, in B- and T-cell function and in disease is discussed. The potential therapeutic benefits of blocking LT/LIGHT signalling is also discussed. Much of the efficiency of the immune system is attributed to the high degree of spatial and temporal organization in the secondary lymphoid organs. Signalling through the lymphotoxin (LT) pathway is a crucial element in the maintenance of this organized Microenvironment. The effect of altering lymphoid Microenvironments on immune responses remains relatively unexplored. Inhibitors of the LT and LIGHT pathways have been shown to reduce disease in a wide range of autoimmune models. This approach has provided a tool to probe the effect of manipulation of the Microenvironment on both normal and pathological immune responses.

Eun Sung Park - One of the best experts on this subject based on the ideXlab platform.

  • abstract 4283 cross species hybridization of microarrays for studying tumor transcriptome of brain metastasis
    Cancer Research, 2012
    Co-Authors: Eun Sung Park, Sun Jin Kim, Seung Wook Kim, Se Lyun Yoon, Sun Hee Leem, Sang Bae Kim, Soo Mi Kim, Yun Yong Park, Jae Ho Cheong, Hyun Goo Woo
    Abstract:

    Although the importance of the cellular Microenvironment (soil) during invasion and metastasis of cancer cells (seed) has been well-recognized, technical challenges have limited the ability to assess the influence of the Microenvironment on cancer cells at the molecular level. Here, we show that an experimental strategy, competitive cross-species hybridization of microarray experiments, can characterize the influence of different Microenvironments on cancer cells by independently extracting gene expression data of cancer and host cells when human cancer cells were xenografted into different organ sites of immunocompromised mice. Surprisingly, the analysis of gene expression data showed that the brain Microenvironment induces complete reprogramming of metastasized cancer cells, resulting in a gain of neuronal cell characteristics and mimicking neurogenesis during development. We also show that epigenetic changes coincide with transcriptional reprogramming in cancer cells. These observations provide proof of principle for competitive cross-species hybridization of microarray experiments to characterize the effect of the Microenvironment on tumor cell behavior Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4283. doi:1538-7445.AM2012-4283

  • cross species hybridization of microarrays for studying tumor transcriptome of brain metastasis
    Proceedings of the National Academy of Sciences of the United States of America, 2011
    Co-Authors: Eun Sung Park, Sun Jin Kim, Seung Wook Kim, Se Lyun Yoon, Sun Hee Leem, Sang Bae Kim, Soo Mi Kim, Yun Yong Park, Jae Ho Cheong, Hyun Goo Woo
    Abstract:

    Although the importance of the cellular Microenvironment (soil) during invasion and metastasis of cancer cells (seed) has been well-recognized, technical challenges have limited the ability to assess the influence of the Microenvironment on cancer cells at the molecular level. Here, we show that an experimental strategy, competitive cross-species hybridization of microarray experiments, can characterize the influence of different Microenvironments on cancer cells by independently extracting gene expression data of cancer and host cells when human cancer cells were xenografted into different organ sites of immunocompromised mice. Surprisingly, the analysis of gene expression data showed that the brain Microenvironment induces complete reprogramming of metastasized cancer cells, resulting in a gain of neuronal cell characteristics and mimicking neurogenesis during development. We also show that epigenetic changes coincide with transcriptional reprogramming in cancer cells. These observations provide proof of principle for competitive cross-species hybridization of microarray experiments to characterize the effect of the Microenvironment on tumor cell behavior.

Ji Sun Choi - One of the best experts on this subject based on the ideXlab platform.

  • Challenges and Opportunities to Harnessing the (Hematopoietic) Stem Cell Niche
    Stem cell reports, 2016
    Co-Authors: Ji Sun Choi, Brendan A C Harley
    Abstract:

    In our body, stem cells reside in a Microenvironment termed the niche. While the exact composition and, therefore, the level of complexity of a stem cell niche can vary significantly tissue-to-tissue, the stem cell niche Microenvironment is dynamic, typically containing spatial and temporal variations in both cellular, extracellular matrix, and biomolecular components. This complex flow of secreted or bound biomolecules, cytokines, extracellular matrix components, and cellular constituents all contributes to the regulation of stem cell fate specification events, making engineering approaches at the nanoscale and microscale of particular interest for creating an artificial niche environment in vitro. Recent advances in fabrication approaches have enabled biomedical researchers to capture and recreate the complexity of stem cell niche Microenvironments in vitro. Such engineered platforms show promise as a means to enhance our understanding of the mechanisms underlying niche-mediated stem cell regulation as well as offer opportunities to precisely control stem cell expansion and differentiation events for clinical applications. While these principles generally apply to all adult stem cells and niches, in this review, we focus on recent developments in engineering synthetic niche Microenvironments for one of the best-characterized stem cell populations, hematopoietic stem cells (HSCs). Specifically, we highlight recent advances in platforms designed to facilitate the extrinsic control of HSC fate decisions.

  • Challenges and Opportunities to Harnessing the (Hematopoietic) Stem Cell Niche
    Current stem cell reports, 2016
    Co-Authors: Ji Sun Choi, Brendan A C Harley
    Abstract:

    In our body, stem cells reside in a Microenvironment termed the niche. While the exact composition and therefore the level of complexity of a stem cell niche can vary significantly tissue-to-tissue, the stem cell niche Microenvironment is dynamic, typically containing spatial and temporal variations in both cellular, extracellular matrix, and biomolecular components. This complex flow of secreted or bound biomolecules, cytokines, extracellular matrix components, and cellular constituents all contribute to the regulation of stem cell fate specification events, making engineering approaches at the nano- and micro-scale of particular interest for creating an artificial niche environment in vitro. Recent advances in fabrication approaches have enabled biomedical researchers to capture and recreate the complexity of stem cell niche Microenvironments in vitro. Such engineered platforms show promise as a means to enhance our understanding of the mechanisms underlying niche-mediated stem cell regulation as well as offer opportunities to precisely control stem cell expansion and differentiation events for clinical applications. While these principles generally apply to all adult stem cells and niches, in this review, we focus on recent developments in engineering synthetic niche Microenvironments for one of the best-characterized stem cell populations, hematopoietic stem cells (HSC). Specifically, we highlight recent advances in platforms designed to facilitate the extrinsic control of HSC fate decisions.

  • The combined influence of substrate elasticity and ligand density on the viability and biophysical properties of hematopoietic stem and progenitor cells.
    Biomaterials, 2012
    Co-Authors: Ji Sun Choi, Brendan A C Harley
    Abstract:

    Hematopoietic stem cells (HSCs) are adult stem cells with the capacity to give rise to all blood and immune cells in the body. HSCs are housed in a specialized Microenvironment known as the stem cell niche, which provides intrinsic and extrinsic signals to regulate HSC fate: quiescence, self-renewal, differentiation, mobilization, homing, and apoptosis. These niches provide a complex, three dimensional (3D) Microenvironment consisting of cells, the extracellular matrix (ECM), and ECM-bound or soluble biomolecules that provides cellular, structural, and molecular signals that regulate HSC fate decisions. In this study, we examined the decoupled effects of substrate elasticity, construct dimensionality, and ligand concentration on the biophysical properties of primary hematopoietic stem and progenitor cells (HSPCs) using homologous series of two and three dimensional Microenvironments. Microenvironments were chosen to span the range of biophysical environments presented physiologically within the bone marrow, ranging from soft marrow and adipose tissue ( 30 kPa). We additionally investigated the influence of collagen ligand density on HSPC biophysical parameters and compared these behaviors to those observed in HSPCs grown in culture on stiff glass substrates. This work suggests the potential for substrate stiffness and ligand density to directly affect the biophysical properties of primary hematopoietic stem and progenitor cells at the single cell level and that these parameters may be critical design criteria for the development of artificial HSC niches.