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  1. Article ; Online: Arid1a restrains Kras-dependent changes in acinar cell identity

    Geulah Livshits / Direna Alonso-Curbelo / John P Morris IV / Richard Koche / Michael Saborowski / John Erby Wilkinson / Scott W Lowe

    eLife, Vol

    2018  Volume 7

    Abstract: Mutations in members of the SWI/SNF chromatin remodeling family are common events in cancer, but the mechanisms whereby disruption of SWI/SNF components alters tumorigenesis remain poorly understood. To model the effect of loss of function mutations in ... ...

    Abstract Mutations in members of the SWI/SNF chromatin remodeling family are common events in cancer, but the mechanisms whereby disruption of SWI/SNF components alters tumorigenesis remain poorly understood. To model the effect of loss of function mutations in the SWI/SNF subunit Arid1a in pancreatic ductal adenocarcinoma (PDAC) initiation, we directed shRNA triggered, inducible and reversible suppression of Arid1a to the mouse pancreas in the setting of oncogenic KrasG12D. Arid1a cooperates with Kras in the adult pancreas as postnatal silencing of Arid1a following sustained KrasG12D expression induces rapid and irreversible reprogramming of acinar cells into mucinous PDAC precursor lesions. In contrast, Arid1a silencing during embryogenesis, concurrent with KrasG12D activation, leads to retention of acinar cell fate. Together, our results demonstrate Arid1a as a critical modulator of Kras-dependent changes in acinar cell identity, and underscore an unanticipated influence of timing and genetic context on the effects of SWI/SNF complex alterations in epithelial tumorigenesis.
    Keywords pancreas cancer ; SWI/SNF ; acinar cell ; mouse model ; RNAi ; plasticity ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2018-07-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article: Using CRISPR/Cas to study gene function and model disease in vivo

    Tschaharganeh, Darjus F / Geulah Livshits / Ralph J. Garippa / Scott W. Lowe

    FEBS journal. 2016 Sept., v. 283, no. 17

    2016  

    Abstract: The recent discovery of the CRISPR/Cas system and repurposing of this technology to edit a variety of different genomes have revolutionized an array of scientific fields, from genetics and translational research, to agriculture and bioproduction. In ... ...

    Abstract The recent discovery of the CRISPR/Cas system and repurposing of this technology to edit a variety of different genomes have revolutionized an array of scientific fields, from genetics and translational research, to agriculture and bioproduction. In particular, the prospect of rapid and precise genome editing in laboratory animals by CRISPR/Cas has generated an immense interest in the scientific community. Here we review current in vivo applications of CRISPR/Cas and how this technology can improve our knowledge of gene function and our understanding of biological processes in animal models.
    Keywords animal models ; disease models ; genes ; genetics ; laboratory animals
    Language English
    Dates of publication 2016-09
    Size p. 3194-3203.
    Publishing place John Wiley & Sons, Ltd
    Document type Article
    Note REVIEW
    ZDB-ID 2173655-8
    ISSN 1742-4658 ; 1742-464X
    ISSN (online) 1742-4658
    ISSN 1742-464X
    DOI 10.1111/febs.13750
    Database NAL-Catalogue (AGRICOLA)

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