The Experts below are selected from a list of 264 Experts worldwide ranked by ideXlab platform

Kristiaan J. Lenos - One of the best experts on this subject based on the ideXlab platform.

  • a marker independent lineage tracing system to quantify clonal dynamics and stem Cell Functionality in cancer tissue
    Nature Protocols, 2019
    Co-Authors: Kristiaan J. Lenos, Daniël M. Miedema, Sophie C. Lodestijn, Scott K Lyons, Maarten F Bijlsma, Louis Vermeulen
    Abstract:

    Lineage tracing is a powerful tool that can be used to uncover Cell fates. Here, we describe a novel method for the quantitative analysis of clonal dynamics in grafted cancer tissues. The protocol involves the preparation and validation of Cells for lineage tracing, establishment of grafts and label induction, analysis of clone-size distribution and fitting of the experimental data to a mathematical tumor growth model. In contrast to other lineage-tracing strategies, the method described here assesses stem Cell Functionality and infers tumor expansion dynamics independently of molecular markers such as putative cancer stem Cell (CSC)-specific genes. The experimental system and analytical framework presented can be used to quantify clonal advantages that specific mutations provide, in both the absence and presence of (targeted) therapeutic agents. This protocol typically takes ~20 weeks to complete from Cell line selection to inference of growth dynamics, depending on the grafted cancer growth rate.

  • Stem Cell Functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer
    Nature Cell Biology, 2018
    Co-Authors: Kristiaan J. Lenos, Daniël M. Miedema, Sophie C. Lodestijn, Lisanne E. Nijman, Tom Bosch, Xavier Romero Ros, Filipe C. Lourenço, Maria C. Lecca, Maartje Heijden, Sanne M. Neerven
    Abstract:

    Lenos et al. report that the spatiotemporal regulation of stem Cell Functionality is not intrinsically determined but environmentally defined during tumour growth and drug response in colon cancer.AbstractSolid malignancies have been speculated to depend on cancer stem Cells (CSCs) for expansion and relapse after therapy. Here we report on quantitative analyses of lineage tracing data from primary colon cancer xenograft tissue to assess CSC Functionality in a human solid malignancy. The temporally obtained clone size distribution data support a model in which stem Cell function in established cancers is not intrinsically, but is entirely spatiotemporally orchestrated. Functional stem Cells that drive tumour expansion predominantly reside at the tumour edge, close to cancer-associated fibroblasts. Hence, stem Cell properties change in time depending on the Cell location. Furthermore, although chemotherapy enriches for Cells with a CSC phenotype, in this context functional stem Cell properties are also fully defined by the microenvironment. To conclude, we identified osteopontin as a key cancer-associated fibroblast-produced factor that drives in situ clonogenicity in colon cancer.

  • stem Cell Functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer
    Nature Cell Biology, 2018
    Co-Authors: Kristiaan J. Lenos, Daniël M. Miedema, Sophie C. Lodestijn, Lisanne E. Nijman, Tom Bosch, Filipe C. Lourenço, Maria C. Lecca, Maartje Heijden, Sanne M. Neerven, Anita Van Oort
    Abstract:

    Solid malignancies have been speculated to depend on cancer stem Cells (CSCs) for expansion and relapse after therapy. Here we report on quantitative analyses of lineage tracing data from primary colon cancer xenograft tissue to assess CSC Functionality in a human solid malignancy. The temporally obtained clone size distribution data support a model in which stem Cell function in established cancers is not intrinsically, but is entirely spatiotemporally orchestrated. Functional stem Cells that drive tumour expansion predominantly reside at the tumour edge, close to cancer-associated fibroblasts. Hence, stem Cell properties change in time depending on the Cell location. Furthermore, although chemotherapy enriches for Cells with a CSC phenotype, in this context functional stem Cell properties are also fully defined by the microenvironment. To conclude, we identified osteopontin as a key cancer-associated fibroblast-produced factor that drives in situ clonogenicity in colon cancer.

Sanne M. Neerven - One of the best experts on this subject based on the ideXlab platform.

  • Stem Cell Functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer
    Nature Cell Biology, 2018
    Co-Authors: Kristiaan J. Lenos, Daniël M. Miedema, Sophie C. Lodestijn, Lisanne E. Nijman, Tom Bosch, Xavier Romero Ros, Filipe C. Lourenço, Maria C. Lecca, Maartje Heijden, Sanne M. Neerven
    Abstract:

    Lenos et al. report that the spatiotemporal regulation of stem Cell Functionality is not intrinsically determined but environmentally defined during tumour growth and drug response in colon cancer.AbstractSolid malignancies have been speculated to depend on cancer stem Cells (CSCs) for expansion and relapse after therapy. Here we report on quantitative analyses of lineage tracing data from primary colon cancer xenograft tissue to assess CSC Functionality in a human solid malignancy. The temporally obtained clone size distribution data support a model in which stem Cell function in established cancers is not intrinsically, but is entirely spatiotemporally orchestrated. Functional stem Cells that drive tumour expansion predominantly reside at the tumour edge, close to cancer-associated fibroblasts. Hence, stem Cell properties change in time depending on the Cell location. Furthermore, although chemotherapy enriches for Cells with a CSC phenotype, in this context functional stem Cell properties are also fully defined by the microenvironment. To conclude, we identified osteopontin as a key cancer-associated fibroblast-produced factor that drives in situ clonogenicity in colon cancer.

  • stem Cell Functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer
    Nature Cell Biology, 2018
    Co-Authors: Kristiaan J. Lenos, Daniël M. Miedema, Sophie C. Lodestijn, Lisanne E. Nijman, Tom Bosch, Filipe C. Lourenço, Maria C. Lecca, Maartje Heijden, Sanne M. Neerven, Anita Van Oort
    Abstract:

    Solid malignancies have been speculated to depend on cancer stem Cells (CSCs) for expansion and relapse after therapy. Here we report on quantitative analyses of lineage tracing data from primary colon cancer xenograft tissue to assess CSC Functionality in a human solid malignancy. The temporally obtained clone size distribution data support a model in which stem Cell function in established cancers is not intrinsically, but is entirely spatiotemporally orchestrated. Functional stem Cells that drive tumour expansion predominantly reside at the tumour edge, close to cancer-associated fibroblasts. Hence, stem Cell properties change in time depending on the Cell location. Furthermore, although chemotherapy enriches for Cells with a CSC phenotype, in this context functional stem Cell properties are also fully defined by the microenvironment. To conclude, we identified osteopontin as a key cancer-associated fibroblast-produced factor that drives in situ clonogenicity in colon cancer.

Sophie C. Lodestijn - One of the best experts on this subject based on the ideXlab platform.

  • a marker independent lineage tracing system to quantify clonal dynamics and stem Cell Functionality in cancer tissue
    Nature Protocols, 2019
    Co-Authors: Kristiaan J. Lenos, Daniël M. Miedema, Sophie C. Lodestijn, Scott K Lyons, Maarten F Bijlsma, Louis Vermeulen
    Abstract:

    Lineage tracing is a powerful tool that can be used to uncover Cell fates. Here, we describe a novel method for the quantitative analysis of clonal dynamics in grafted cancer tissues. The protocol involves the preparation and validation of Cells for lineage tracing, establishment of grafts and label induction, analysis of clone-size distribution and fitting of the experimental data to a mathematical tumor growth model. In contrast to other lineage-tracing strategies, the method described here assesses stem Cell Functionality and infers tumor expansion dynamics independently of molecular markers such as putative cancer stem Cell (CSC)-specific genes. The experimental system and analytical framework presented can be used to quantify clonal advantages that specific mutations provide, in both the absence and presence of (targeted) therapeutic agents. This protocol typically takes ~20 weeks to complete from Cell line selection to inference of growth dynamics, depending on the grafted cancer growth rate.

  • Stem Cell Functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer
    Nature Cell Biology, 2018
    Co-Authors: Kristiaan J. Lenos, Daniël M. Miedema, Sophie C. Lodestijn, Lisanne E. Nijman, Tom Bosch, Xavier Romero Ros, Filipe C. Lourenço, Maria C. Lecca, Maartje Heijden, Sanne M. Neerven
    Abstract:

    Lenos et al. report that the spatiotemporal regulation of stem Cell Functionality is not intrinsically determined but environmentally defined during tumour growth and drug response in colon cancer.AbstractSolid malignancies have been speculated to depend on cancer stem Cells (CSCs) for expansion and relapse after therapy. Here we report on quantitative analyses of lineage tracing data from primary colon cancer xenograft tissue to assess CSC Functionality in a human solid malignancy. The temporally obtained clone size distribution data support a model in which stem Cell function in established cancers is not intrinsically, but is entirely spatiotemporally orchestrated. Functional stem Cells that drive tumour expansion predominantly reside at the tumour edge, close to cancer-associated fibroblasts. Hence, stem Cell properties change in time depending on the Cell location. Furthermore, although chemotherapy enriches for Cells with a CSC phenotype, in this context functional stem Cell properties are also fully defined by the microenvironment. To conclude, we identified osteopontin as a key cancer-associated fibroblast-produced factor that drives in situ clonogenicity in colon cancer.

  • stem Cell Functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer
    Nature Cell Biology, 2018
    Co-Authors: Kristiaan J. Lenos, Daniël M. Miedema, Sophie C. Lodestijn, Lisanne E. Nijman, Tom Bosch, Filipe C. Lourenço, Maria C. Lecca, Maartje Heijden, Sanne M. Neerven, Anita Van Oort
    Abstract:

    Solid malignancies have been speculated to depend on cancer stem Cells (CSCs) for expansion and relapse after therapy. Here we report on quantitative analyses of lineage tracing data from primary colon cancer xenograft tissue to assess CSC Functionality in a human solid malignancy. The temporally obtained clone size distribution data support a model in which stem Cell function in established cancers is not intrinsically, but is entirely spatiotemporally orchestrated. Functional stem Cells that drive tumour expansion predominantly reside at the tumour edge, close to cancer-associated fibroblasts. Hence, stem Cell properties change in time depending on the Cell location. Furthermore, although chemotherapy enriches for Cells with a CSC phenotype, in this context functional stem Cell properties are also fully defined by the microenvironment. To conclude, we identified osteopontin as a key cancer-associated fibroblast-produced factor that drives in situ clonogenicity in colon cancer.

Daniël M. Miedema - One of the best experts on this subject based on the ideXlab platform.

  • a marker independent lineage tracing system to quantify clonal dynamics and stem Cell Functionality in cancer tissue
    Nature Protocols, 2019
    Co-Authors: Kristiaan J. Lenos, Daniël M. Miedema, Sophie C. Lodestijn, Scott K Lyons, Maarten F Bijlsma, Louis Vermeulen
    Abstract:

    Lineage tracing is a powerful tool that can be used to uncover Cell fates. Here, we describe a novel method for the quantitative analysis of clonal dynamics in grafted cancer tissues. The protocol involves the preparation and validation of Cells for lineage tracing, establishment of grafts and label induction, analysis of clone-size distribution and fitting of the experimental data to a mathematical tumor growth model. In contrast to other lineage-tracing strategies, the method described here assesses stem Cell Functionality and infers tumor expansion dynamics independently of molecular markers such as putative cancer stem Cell (CSC)-specific genes. The experimental system and analytical framework presented can be used to quantify clonal advantages that specific mutations provide, in both the absence and presence of (targeted) therapeutic agents. This protocol typically takes ~20 weeks to complete from Cell line selection to inference of growth dynamics, depending on the grafted cancer growth rate.

  • Stem Cell Functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer
    Nature Cell Biology, 2018
    Co-Authors: Kristiaan J. Lenos, Daniël M. Miedema, Sophie C. Lodestijn, Lisanne E. Nijman, Tom Bosch, Xavier Romero Ros, Filipe C. Lourenço, Maria C. Lecca, Maartje Heijden, Sanne M. Neerven
    Abstract:

    Lenos et al. report that the spatiotemporal regulation of stem Cell Functionality is not intrinsically determined but environmentally defined during tumour growth and drug response in colon cancer.AbstractSolid malignancies have been speculated to depend on cancer stem Cells (CSCs) for expansion and relapse after therapy. Here we report on quantitative analyses of lineage tracing data from primary colon cancer xenograft tissue to assess CSC Functionality in a human solid malignancy. The temporally obtained clone size distribution data support a model in which stem Cell function in established cancers is not intrinsically, but is entirely spatiotemporally orchestrated. Functional stem Cells that drive tumour expansion predominantly reside at the tumour edge, close to cancer-associated fibroblasts. Hence, stem Cell properties change in time depending on the Cell location. Furthermore, although chemotherapy enriches for Cells with a CSC phenotype, in this context functional stem Cell properties are also fully defined by the microenvironment. To conclude, we identified osteopontin as a key cancer-associated fibroblast-produced factor that drives in situ clonogenicity in colon cancer.

  • stem Cell Functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer
    Nature Cell Biology, 2018
    Co-Authors: Kristiaan J. Lenos, Daniël M. Miedema, Sophie C. Lodestijn, Lisanne E. Nijman, Tom Bosch, Filipe C. Lourenço, Maria C. Lecca, Maartje Heijden, Sanne M. Neerven, Anita Van Oort
    Abstract:

    Solid malignancies have been speculated to depend on cancer stem Cells (CSCs) for expansion and relapse after therapy. Here we report on quantitative analyses of lineage tracing data from primary colon cancer xenograft tissue to assess CSC Functionality in a human solid malignancy. The temporally obtained clone size distribution data support a model in which stem Cell function in established cancers is not intrinsically, but is entirely spatiotemporally orchestrated. Functional stem Cells that drive tumour expansion predominantly reside at the tumour edge, close to cancer-associated fibroblasts. Hence, stem Cell properties change in time depending on the Cell location. Furthermore, although chemotherapy enriches for Cells with a CSC phenotype, in this context functional stem Cell properties are also fully defined by the microenvironment. To conclude, we identified osteopontin as a key cancer-associated fibroblast-produced factor that drives in situ clonogenicity in colon cancer.

Björn Schumacher - One of the best experts on this subject based on the ideXlab platform.

  • Impact of genomic damage and ageing on stem Cell function
    Nature Cell Biology, 2014
    Co-Authors: Axel Behrens, K. Lenhard Rudolph, Jan M. Van Deursen, Björn Schumacher
    Abstract:

    Impairment of stem Cell function contributes to the progressive deterioration of tissue maintenance and repair with ageing. Evidence is mounting that age-dependent accumulation of DNA damage in both stem Cells and Cells that comprise the stem Cell microenvironment are partly responsible for stem Cell dysfunction with ageing. Here, we review the impact of the various types of DNA damage that accumulate with ageing on stem Cell Functionality, as well as the development of cancer. We discuss DNA-damage-induced Cell intrinsic and extrinsic alterations that influence these processes, and review recent advances in understanding systemic adjustments to DNA damage and how they affect stem Cells. In the second Review in our Genomic Instability series, Rudolph and colleagues discuss how the genomic damage that accumulates during ageing affects stem Cell function through both Cell-intrinsic and Cell-extrinsic mechanisms.

  • Impact of genomic damage and ageing on stem Cell function
    Nature Cell Biology, 2014
    Co-Authors: Axel Behrens, K. Lenhard Rudolph, Jan M. Van Deursen, Björn Schumacher
    Abstract:

    Impairment of stem Cell function contributes to the progressive deterioration of tissue maintenance and repair with ageing. Evidence is mounting that age-dependent accumulation of DNA damage in both stem Cells and Cells that comprise the stem Cell microenvironment are partly responsible for stem Cell dysfunction with ageing. Here, we review the impact of the various types of DNA damage that accumulate with ageing on stem Cell Functionality, as well as the development of cancer. We discuss DNA-damage-induced Cell intrinsic and extrinsic alterations that influence these processes, and review recent advances in understanding systemic adjustments to DNA damage and how they affect stem Cells.