KUKU

KU ScholarWorks

  • myKU
  • Email
  • Enroll & Pay
  • KU Directory
    • Login
    View Item 
    •   KU ScholarWorks
    • Dissertations and Theses
    • Dissertations
    • View Item
    •   KU ScholarWorks
    • Dissertations and Theses
    • Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Beta-catenin Associated Protein Complex Maintains Ground State Mouse Embryonic Stem Cell by Regulating Germline Development

    Thumbnail
    View/Open
    TAO_ku_0099D_15041_DATA_1.pdf (240.6Mb)
    Issue Date
    2016-12-31
    Author
    Tao, Fang
    Publisher
    University of Kansas
    Format
    98 pages
    Type
    Dissertation
    Degree Level
    Ph.D.
    Discipline
    Pathology & Laboratory Medicine
    Rights
    Copyright held by the author.
    Metadata
    Show full item record
    Abstract
    Mouse embryonic stem (ES) cells cultured in defined medium with MEK and GSK3 inhibitors(2i) resemble the pre-implantation epiblast in the ground state, with full development capacity including the somatic lineages and the germline. Although beta- catenin is known to be crucial for naive pluripotency of ES cells, the mechanism is not fully understood. Here I show that beta-catenin interacts with a repressive protein complex to maintain the ground state of ES cells by fine-tuning the germline development potential of ES cells. I use the mouse ES cell to show that absence of beta-catenin impairs ES cell self-renewal without affecting the core self-renewal circuitry of Oct4, Sox2 and Nanog as well as other pluripotency factors. However, beta-catenin-deficient cells show a primed state transcriptional signature with perturbed gene expression of germline and neuronal lineage. Knockdown of Tcf7l1, the repressor in canonical Wnt signaling pathway, does not completely rescue the beta-catenin-deficient phenotype of ES cells. Mechanistically, beta-catenin forms a novel biochemical complex with E2F6, HP1gamma and HMGA2 to restrain ES cells from differentiation by co-occupying the promoter of germline and neuronal lineage regulators independent of TCF7L1. Moreover, beta-catenin functions differentially in early and late germ cell development, and keeps balance with E2F6 to prevent premature meiosis initiation in ES cells. Overall, my study shows that beta-catenin forms a repressive protein complex with E2F6, HP1gamma and HMGA2 to maintain ground state by orchestrating the development plasticity of ES cells.
    URI
    http://hdl.handle.net/1808/24803
    Collections
    • Dissertations [4625]
    • KU Med Center Dissertations and Theses [464]

    Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.


    We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.


    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    Browse

    All of KU ScholarWorksCommunities & CollectionsThis Collection

    My Account

    Login

    Statistics

    View Usage Statistics

    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    The University of Kansas
      Contact KU ScholarWorks
    Lawrence, KS | Maps
     
    • Academics
    • Admission
    • Alumni
    • Athletics
    • Campuses
    • Giving
    • Jobs

    The University of Kansas prohibits discrimination on the basis of race, color, ethnicity, religion, sex, national origin, age, ancestry, disability, status as a veteran, sexual orientation, marital status, parental status, gender identity, gender expression and genetic information in the University’s programs and activities. The following person has been designated to handle inquiries regarding the non-discrimination policies: Director of the Office of Institutional Opportunity and Access, IOA@ku.edu, 1246 W. Campus Road, Room 153A, Lawrence, KS, 66045, (785)864-6414, 711 TTY.

     Contact KU
    Lawrence, KS | Maps