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  1. Article ; Online: Diverse transcriptional regulation and functional effects revealed by CRISPR/Cas9-directed epigenetic editing.

    Vizoso, Miguel / van Rheenen, Jacco

    Oncotarget

    2021  Volume 12, Issue 17, Page(s) 1651–1662

    Abstract: DNA methylation is an epigenetic process that controls DNA accessibility and serves as a transcriptomic switch when deposited at regulatory regions. The adequate functioning of this process is indispensable for tissue homeostasis and cell fate ... ...

    Abstract DNA methylation is an epigenetic process that controls DNA accessibility and serves as a transcriptomic switch when deposited at regulatory regions. The adequate functioning of this process is indispensable for tissue homeostasis and cell fate determination. Conversely, altered DNA methylation patterns result in abnormal gene transcription profiles that contribute to tumor initiation and progression. However, whether the consequence of DNA methylation on gene expression and cell fate is uniform regardless of the cell type or state could so far not been tested due to the lack of technologies to target DNA methylation
    Language English
    Publishing date 2021-08-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2560162-3
    ISSN 1949-2553 ; 1949-2553
    ISSN (online) 1949-2553
    ISSN 1949-2553
    DOI 10.18632/oncotarget.28037
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Multidimensional Imaging of Breast Cancer.

    Rios, Anne C / van Rheenen, Jacco / Scheele, Colinda L G J

    Cold Spring Harbor perspectives in medicine

    2023  Volume 13, Issue 5

    Abstract: Breast cancer is a pathological condition characterized by high morphological and molecular heterogeneity. Not only the breast cancer cells, but also their tumor micro-environment consists of a multitude of cell types and states, which continuously ... ...

    Abstract Breast cancer is a pathological condition characterized by high morphological and molecular heterogeneity. Not only the breast cancer cells, but also their tumor micro-environment consists of a multitude of cell types and states, which continuously evolve throughout progression of the disease. To understand breast cancer evolution within this complex environment, in situ analysis of breast cancer and their co-evolving cells and structures in space and time are essential. In this review, recent technical advances in three-dimensional (3D) and intravital imaging of breast cancer are discussed. Moreover, we highlight the resulting new knowledge on breast cancer biology obtained through these innovative imaging technologies. Finally, we discuss how multidimensional imaging technologies can be integrated with molecular profiling to understand the full complexity of breast cancer and the tumor micro-environment during tumor progression and treatment response.
    MeSH term(s) Humans ; Female ; Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Diagnostic Imaging ; Tumor Microenvironment
    Language English
    Publishing date 2023-05-02
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ISSN 2157-1422
    ISSN (online) 2157-1422
    DOI 10.1101/cshperspect.a041330
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Coordinated cancer chaos.

    Messal, Hendrik A / van Rheenen, Jacco

    Cell

    2022  Volume 186, Issue 2, Page(s) 235–237

    Abstract: Stochastic processes, such as genetic instability and microenvironment evolution, drive tumor heterogeneity, thereby creating the chaotic appearance of tumors in histopathology. In this issue of Cell, Lin et al. reveal that tumors are surprisingly ... ...

    Abstract Stochastic processes, such as genetic instability and microenvironment evolution, drive tumor heterogeneity, thereby creating the chaotic appearance of tumors in histopathology. In this issue of Cell, Lin et al. reveal that tumors are surprisingly spatially organized from a molecular to tissue scale, indicating that cancers evolve as autonomously patterned systems.
    MeSH term(s) Humans ; Nonlinear Dynamics ; Neoplasms/genetics ; Neoplasms/pathology ; Tumor Microenvironment
    Language English
    Publishing date 2022-11-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2022.12.015
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1167: Show issues Location:
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    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 58: Show issues

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  4. Article: Epithelial-to-Mesenchymal Transition in the Light of Plasticity and Hybrid E/M States.

    Bornes, Laura / Belthier, Guillaume / van Rheenen, Jacco

    Journal of clinical medicine

    2021  Volume 10, Issue 11

    Abstract: Epithelial-to-mesenchymal transition (EMT) is a cellular program which leads to cells losing epithelial features, including cell polarity, cell-cell adhesion and attachment to the basement membrane, while gaining mesenchymal characteristics, such as ... ...

    Abstract Epithelial-to-mesenchymal transition (EMT) is a cellular program which leads to cells losing epithelial features, including cell polarity, cell-cell adhesion and attachment to the basement membrane, while gaining mesenchymal characteristics, such as invasive properties and stemness. This program is involved in embryogenesis, wound healing and cancer progression. Over the years, the role of EMT in cancer progression has been heavily debated, and the requirement of this process in metastasis even has been disputed. In this review, we discuss previous discrepancies in the light of recent findings on EMT, plasticity and hybrid E/M states. Moreover, we highlight various tumor microenvironmental cues and cell intrinsic signaling pathways that induce and sustain EMT programs, plasticity and hybrid E/M states. Lastly, we discuss how recent findings on plasticity, especially on those that enable cells to switch between hybrid E/M states, have changed our understanding on the role of EMT in cancer metastasis, stemness and therapy resistance.
    Language English
    Publishing date 2021-05-29
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2662592-1
    ISSN 2077-0383
    ISSN 2077-0383
    DOI 10.3390/jcm10112403
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Intravital microscopy to illuminate cell state plasticity during metastasis.

    van Rheenen, Jacco / Scheele, Colinda L G J

    Current opinion in cell biology

    2021  Volume 72, Page(s) 28–35

    Abstract: Microenvironmental cues in tumors induce in a wide variety of cellular states that subsequently lead to cancer cells with distinct cellular identity, behavior, and fate. Recent literature suggests that the ability to change cellular states, a process ... ...

    Abstract Microenvironmental cues in tumors induce in a wide variety of cellular states that subsequently lead to cancer cells with distinct cellular identity, behavior, and fate. Recent literature suggests that the ability to change cellular states, a process defined as cell state plasticity, enable cells to rapidly adapt to their changing environment during tumor progression and metastasis. In this review, we will discuss how recent high-resolution intravital microscopy studies have been instrumental to reveal the real-time dynamics of tumor cell state plasticity during the different steps of the metastatic cascade. In addition, we will highlight the role of tumor plasticity during anticancer treatment response, and how plasticity can be used as a potential druggable target.
    MeSH term(s) Cell Plasticity ; Humans ; Intravital Microscopy ; Neoplasm Metastasis ; Neoplasms
    Language English
    Publishing date 2021-05-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1026381-0
    ISSN 1879-0410 ; 0955-0674
    ISSN (online) 1879-0410
    ISSN 0955-0674
    DOI 10.1016/j.ceb.2021.04.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2963: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article: Longitudinal intravital microscopy using a mammary imaging window with replaceable lid

    Mourao, Larissa / Ciwinska, Marta / van Rheenen, Jacco / Scheele, Colinda L. G. J.

    Journal of visualized experiments. 2022 Jan. 20, , no. 179

    2022  

    Abstract: The branched structure of the mammary gland is highly dynamic and undergoes several phases of growth and remodeling after birth. Intravital microscopy in combination with skin flap surgery or implantation of imaging windows has been used to study the ... ...

    Abstract The branched structure of the mammary gland is highly dynamic and undergoes several phases of growth and remodeling after birth. Intravital microscopy in combination with skin flap surgery or implantation of imaging windows has been used to study the dynamics of the healthy mammary gland at different developmental stages. Most mammary imaging technologies are limited to a time frame of hours to days, whereas the majority of mammary gland remodeling processes occur in time frames of days to weeks. To study mammary gland remodeling, methods that allow optical access to the tissue of interest for extended time frames are required. Here, an improved version of the titanium mammary imaging window with a replaceable lid (R.MIW) is described that allows high-resolution imaging of the mammary gland with a cellular resolution for up to several weeks. Importantly, the R.MIW provides tissue access over the entire duration of the intravital imaging experiment and could therefore be used for local tissue manipulation, labeling, drug administration, or image-guided microdissection. Taken together, the R.MIW enables high-resolution characterization of the cellular dynamics during mammary gland development, homeostasis, and disease.
    Keywords drugs ; homeostasis ; mammary development ; mammary glands ; microdissection ; microscopy ; surgery ; titanium
    Language English
    Dates of publication 2022-0120
    Size p. e63326.
    Publishing place Journal of Visualized Experiments
    Document type Article
    ZDB-ID 2259946-0
    ISSN 1940-087X
    ISSN 1940-087X
    DOI 10.3791/63326
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: Generation of mixed murine organoids to model cellular interactions.

    Krotenberg Garcia, Ana / van Rheenen, Jacco / Suijkerbuijk, Saskia Jacoba Elisabeth

    STAR protocols

    2021  Volume 2, Issue 4, Page(s) 100997

    Abstract: Cell competition is a mechanism of interaction that dictates cell selection based on differences in cellular fitness. We designed a protocol to generate mixed murine organoids and enteroid monolayers used to study such complex cellular interactions in a ... ...

    Abstract Cell competition is a mechanism of interaction that dictates cell selection based on differences in cellular fitness. We designed a protocol to generate mixed murine organoids and enteroid monolayers used to study such complex cellular interactions in a mammalian system. This protocol is dedicated to follow the behavior of different cell populations over time, using (time-lapse) microscopy or transcriptome/proteome analysis. For complete details on the use and execution of this protocol, please refer to Krotenberg Garcia et al. (2021).
    MeSH term(s) Animals ; Cell Communication/physiology ; Cell Culture Techniques ; Cells, Cultured ; Mice ; Organoids/cytology ; Tissue Culture Techniques/methods
    Language English
    Publishing date 2021-12-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2021.100997
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: An Intravital Microscopy Toolbox to Study Mammary Gland Dynamics from Cellular Level to Organ Scale.

    Messal, Hendrik A / van Rheenen, Jacco / Scheele, Colinda L G J

    Journal of mammary gland biology and neoplasia

    2021  Volume 26, Issue 1, Page(s) 9–27

    Abstract: The architecture of the mouse mammary gland is highly dynamic and constantly remodeled during pubertal development and estrous cycle-driven sprouting and regression of alveolar side branches. During each of these developmental stages, turnover is driven ... ...

    Abstract The architecture of the mouse mammary gland is highly dynamic and constantly remodeled during pubertal development and estrous cycle-driven sprouting and regression of alveolar side branches. During each of these developmental stages, turnover is driven by distinct subsets of mammary epithelial cells. Extensive previous research has shed light on the unique morphological and cell biological characteristics of each stage. However, technological shortcomings failed to capture the dynamics and single-cell contributions to mammary remodeling. Here, we developed in vivo imaging strategies to follow the same mammary ducts over time and quantify the dynamics of mammary gland growth and remodeling from single-cell level to organ scale. Using a combination of intravital microscopy and genetic reporter systems we show how proliferative heterogeneity drives ductal morphogenesis during different developmental stages. To visualize pubertal growth at the cellular level, we performed long-term time-lapse imaging of extending terminal end buds through a mammary imaging window. We show that single-cells within the terminal end buds are extremely motile and continuously exchange position whilst the duct is elongating. To visualize short-term remodeling in the adult mammary gland at the single cell level, we performed multi-day intravital imaging in photoconvertible Kikume Green-Red mice and fluorescent ubiquitination-based cell cycle indicator mice. We demonstrate that the contribution of single-cells to estrous-driven remodeling is highly variable between cells in the same micro-environment. To assess the effects of this dynamic proliferative contribution on the long-term stability of tissue architecture, we developed a repeated skin flap method to assess mammary gland morphology by intravital microscopy over extended time spans for up to six months. Interestingly, in contrast to the short-term dynamic remodeling, the long-term morphology of the mammary gland remains remarkably stable. Together, our tool box of imaging strategies allows to identify and map transient and continuing dynamics of single cells to the architecture of the mammary gland.
    MeSH term(s) Animals ; Cell Cycle/physiology ; Cell Proliferation/physiology ; Epithelial Cells/cytology ; Epithelial Cells/physiology ; Estrous Cycle/physiology ; Female ; Homeostasis/physiology ; Intravital Microscopy/methods ; Mammary Glands, Animal/cytology ; Mammary Glands, Animal/physiology ; Mice ; Puberty/physiology
    Language English
    Publishing date 2021-05-04
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1327345-0
    ISSN 1573-7039 ; 1083-3021
    ISSN (online) 1573-7039
    ISSN 1083-3021
    DOI 10.1007/s10911-021-09487-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4478: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  9. Article ; Online: Longitudinal Intravital Microscopy Using a Mammary Imaging Window with Replaceable Lid.

    Mourao, Larissa / Ciwinska, Marta / van Rheenen, Jacco / Scheele, Colinda L G J

    Journal of visualized experiments : JoVE

    2022  , Issue 179

    Abstract: The branched structure of the mammary gland is highly dynamic and undergoes several phases of growth and remodeling after birth. Intravital microscopy in combination with skin flap surgery or implantation of imaging windows has been used to study the ... ...

    Abstract The branched structure of the mammary gland is highly dynamic and undergoes several phases of growth and remodeling after birth. Intravital microscopy in combination with skin flap surgery or implantation of imaging windows has been used to study the dynamics of the healthy mammary gland at different developmental stages. Most mammary imaging technologies are limited to a time frame of hours to days, whereas the majority of mammary gland remodeling processes occur in time frames of days to weeks. To study mammary gland remodeling, methods that allow optical access to the tissue of interest for extended time frames are required. Here, an improved version of the titanium mammary imaging window with a replaceable lid (R.MIW) is described that allows high-resolution imaging of the mammary gland with a cellular resolution for up to several weeks. Importantly, the R.MIW provides tissue access over the entire duration of the intravital imaging experiment and could therefore be used for local tissue manipulation, labeling, drug administration, or image-guided microdissection. Taken together, the R.MIW enables high-resolution characterization of the cellular dynamics during mammary gland development, homeostasis, and disease.
    MeSH term(s) Animals ; Homeostasis ; Intravital Microscopy/methods ; Mammary Glands, Animal/diagnostic imaging
    Language English
    Publishing date 2022-01-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
    ZDB-ID 2259946-0
    ISSN 1940-087X ; 1940-087X
    ISSN (online) 1940-087X
    ISSN 1940-087X
    DOI 10.3791/63326
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Tissue architecture in tumor initiation and progression.

    Almagro, Jorge / Messal, Hendrik A / Elosegui-Artola, Alberto / van Rheenen, Jacco / Behrens, Axel

    Trends in cancer

    2022  Volume 8, Issue 6, Page(s) 494–505

    Abstract: The 3D architecture of tissues bearing tumors impacts on the mechanical microenvironment of cancer, the accessibility of stromal cells, and the routes of invasion. A myriad of intrinsic and extrinsic forces exerted by the cancer cells, the host tissue, ... ...

    Abstract The 3D architecture of tissues bearing tumors impacts on the mechanical microenvironment of cancer, the accessibility of stromal cells, and the routes of invasion. A myriad of intrinsic and extrinsic forces exerted by the cancer cells, the host tissue, and the molecular and cellular microenvironment modulate the morphology of the tumor and its malignant potential through mechanical, biochemical, genetic, and epigenetic cues. Recent studies have investigated how tissue architecture influences cancer biology from tumor initiation and progression to distant metastatic seeding and response to therapy. With a focus on carcinoma, the most common type of cancer, this review discusses the latest discoveries on how tumor architecture is built and how tissue morphology affects the biology and progression of cancer cells.
    MeSH term(s) Cell Transformation, Neoplastic/pathology ; Humans ; Neoplasms/genetics ; Neoplasms/pathology ; Stromal Cells/pathology ; Tumor Microenvironment
    Language English
    Publishing date 2022-03-15
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2852626-0
    ISSN 2405-8025 ; 2405-8033 ; 2405-8033
    ISSN (online) 2405-8025 ; 2405-8033
    ISSN 2405-8033
    DOI 10.1016/j.trecan.2022.02.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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