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  1. AU="Larsen, Hjalte L"
  2. AU="António Pinto-Duarte"

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  1. Article ; Online: Reprogramming cellular identity during intestinal regeneration.

    Larsen, Hjalte L / Jensen, Kim B

    Current opinion in genetics & development

    2021  Volume 70, Page(s) 40–47

    Abstract: The intestine is a vital organ mediating absorption of nutrients and water. Following tissue damage, the intestine mounts a remarkable regenerative response by reprogramming cellular identity to facilitate reinstatement of homeostasis. Here we review ... ...

    Abstract The intestine is a vital organ mediating absorption of nutrients and water. Following tissue damage, the intestine mounts a remarkable regenerative response by reprogramming cellular identity to facilitate reinstatement of homeostasis. Here we review recent advances within intestinal regenerative biology and the emerging concept of fetal-like reprogramming, in which the adult intestinal epithelium transiently enters a repair-associated state reminiscent of ontologically pre-existing stages. We focus on molecular mechanisms governing reprogramming of cellular identity via epithelial-mesenchymal crosstalk, and how novel approaches in organoid technologies enable identification and characterisation of cell-autonomous repair responses within epithelial cells. Transitioning from the single-cell level to tissue scale, we discuss clonal selection following regeneration and associated pathological repurcussions such as cancer and chronic inflammatory diseases.
    MeSH term(s) Animals ; Cellular Reprogramming/physiology ; Epithelial Cells ; Humans ; Intestinal Mucosa/cytology ; Intestines/cytology ; Intestines/physiology ; Organoids ; Regeneration/physiology
    Language English
    Publishing date 2021-05-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1077312-5
    ISSN 1879-0380 ; 0959-437X
    ISSN (online) 1879-0380
    ISSN 0959-437X
    DOI 10.1016/j.gde.2021.05.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3240: 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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  2. Article ; Online: An organoid-based CRISPR-Cas9 screen for regulators of intestinal epithelial maturation and cell fate.

    Hansen, Stine L / Larsen, Hjalte L / Pikkupeura, Laura M / Maciag, Grzegorz / Guiu, Jordi / Müller, Iris / Clement, Ditte L / Mueller, Christina / Johansen, Jens Vilstrup / Helin, Kristian / Lerdrup, Mads / Jensen, Kim B

    Science advances

    2023  Volume 9, Issue 28, Page(s) eadg4055

    Abstract: Generation of functionally mature organs requires exquisite control of transcriptional programs governing cell state transitions during development. Despite advances in understanding the behavior of adult intestinal stem cells and their progeny, the ... ...

    Abstract Generation of functionally mature organs requires exquisite control of transcriptional programs governing cell state transitions during development. Despite advances in understanding the behavior of adult intestinal stem cells and their progeny, the transcriptional regulators that control the emergence of the mature intestinal phenotype remain largely unknown. Using mouse fetal and adult small intestinal organoids, we uncover transcriptional differences between the fetal and adult state and identify rare adult-like cells present in fetal organoids. This suggests that fetal organoids have an inherent potential to mature, which is locked by a regulatory program. By implementing a CRISPR-Cas9 screen targeting transcriptional regulators expressed in fetal organoids, we establish
    MeSH term(s) Animals ; Mice ; CRISPR-Cas Systems ; Cell Differentiation/genetics ; Fetus ; Adult Stem Cells ; Organoids
    Language English
    Publishing date 2023-07-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.adg4055
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Transcriptional and epigenomic profiling identifies YAP signaling as a key regulator of intestinal epithelium maturation.

    Pikkupeura, Laura M / Bressan, Raul B / Guiu, Jordi / Chen, Yun / Maimets, Martti / Mayer, Daniela / Schweiger, Pawel J / Hansen, Stine L / Maciag, Grzegorz J / Larsen, Hjalte L / Lõhmussaar, Kadi / Pedersen, Marianne Terndrup / Teves, Joji M Yap / Bornholdt, Jette / Benes, Vladimir / Sandelin, Albin / Jensen, Kim B

    Science advances

    2023  Volume 9, Issue 28, Page(s) eadf9460

    Abstract: During intestinal organogenesis, equipotent epithelial progenitors mature into phenotypically distinct stem cells that are responsible for lifelong maintenance of the tissue. While the morphological changes associated with the transition are well ... ...

    Abstract During intestinal organogenesis, equipotent epithelial progenitors mature into phenotypically distinct stem cells that are responsible for lifelong maintenance of the tissue. While the morphological changes associated with the transition are well characterized, the molecular mechanisms underpinning the maturation process are not fully understood. Here, we leverage intestinal organoid cultures to profile transcriptional, chromatin accessibility, DNA methylation, and three-dimensional (3D) chromatin conformation landscapes in fetal and adult epithelial cells. We observed prominent differences in gene expression and enhancer activity, which are accompanied by local changes in 3D organization, DNA accessibility, and methylation between the two cellular states. Using integrative analyses, we identified sustained Yes-Associated Protein (YAP) transcriptional activity as a major gatekeeper of the immature fetal state. We found the YAP-associated transcriptional network to be regulated at various levels of chromatin organization and likely to be coordinated by changes in extracellular matrix composition. Together, our work highlights the value of unbiased profiling of regulatory landscapes for the identification of key mechanisms underlying tissue maturation.
    MeSH term(s) Adult ; Humans ; Epigenomics ; Intestinal Mucosa ; Intestines ; Epithelium ; Chromatin/genetics
    Chemical Substances Chromatin
    Language English
    Publishing date 2023-07-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.adf9460
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: YAP/TAZ-Dependent Reprogramming of Colonic Epithelium Links ECM Remodeling to Tissue Regeneration.

    Yui, Shiro / Azzolin, Luca / Maimets, Martti / Pedersen, Marianne Terndrup / Fordham, Robert P / Hansen, Stine L / Larsen, Hjalte L / Guiu, Jordi / Alves, Mariana R P / Rundsten, Carsten F / Johansen, Jens V / Li, Yuan / Madsen, Chris D / Nakamura, Tetsuya / Watanabe, Mamoru / Nielsen, Ole H / Schweiger, Pawel J / Piccolo, Stefano / Jensen, Kim B

    Cell stem cell

    2017  Volume 22, Issue 1, Page(s) 35–49.e7

    Abstract: Tissue regeneration requires dynamic cellular adaptation to the wound environment. It is currently unclear how this is orchestrated at the cellular level and how cell fate is affected by severe tissue damage. Here we dissect cell fate transitions during ... ...

    Abstract Tissue regeneration requires dynamic cellular adaptation to the wound environment. It is currently unclear how this is orchestrated at the cellular level and how cell fate is affected by severe tissue damage. Here we dissect cell fate transitions during colonic regeneration in a mouse dextran sulfate sodium (DSS) colitis model, and we demonstrate that the epithelium is transiently reprogrammed into a primitive state. This is characterized by de novo expression of fetal markers as well as suppression of markers for adult stem and differentiated cells. The fate change is orchestrated by remodeling the extracellular matrix (ECM), increased FAK/Src signaling, and ultimately YAP/TAZ activation. In a defined cell culture system recapitulating the extracellular matrix remodeling observed in vivo, we show that a collagen 3D matrix supplemented with Wnt ligands is sufficient to sustain endogenous YAP/TAZ and induce conversion of cell fate. This provides a simple model for tissue regeneration, implicating cellular reprogramming as an essential element.
    MeSH term(s) Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Biomarkers/metabolism ; Cell Cycle Proteins ; Cellular Reprogramming ; Extracellular Matrix/metabolism ; Fetus/metabolism ; Humans ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/pathology ; Mechanotransduction, Cellular ; Mice, Inbred C57BL ; Phosphoproteins/metabolism ; Regeneration ; Signal Transduction ; Transcription, Genetic ; Transcriptional Activation/genetics
    Chemical Substances Adaptor Proteins, Signal Transducing ; Biomarkers ; Cell Cycle Proteins ; Phosphoproteins ; Yap1 protein, mouse
    Language English
    Publishing date 2017-12-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2375354-7
    ISSN 1875-9777 ; 1934-5909
    ISSN (online) 1875-9777
    ISSN 1934-5909
    DOI 10.1016/j.stem.2017.11.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6589: Show issues Location:
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    Zs.MG 75: Show issues

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