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    Myb controls intestinal stem cell genes and self-renewal

    Access Status
    Open access via publisher
    Authors
    Cheasley, D.
    Pereira, L.
    Lightowler, S.
    Vincan, Elizabeth
    Malaterre, J.
    Ramsay, R.
    Date
    2011
    Type
    Journal Article
    
    Metadata
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    Citation
    Cheasley, D. and Pereira, L. and Lightowler, S. and Vincan, E. and Malaterre, J. and Ramsay, R. 2011. Myb controls intestinal stem cell genes and self-renewal. Stem Cells. 29 (12): pp. 2042-2050.
    Source Title
    Stem Cells
    DOI
    10.1002/stem.761
    ISSN
    1066-5099
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/26821
    Collection
    • Curtin Research Publications
    Abstract

    Rapid advances have been made in the understanding of how the highly proliferative gastrointestinal tract epithelium is regulated under homeostasis and disease. The identification of putative intestinal stem cell (ISC) genes and the ability to culture ISC capable of generating all four lineages plus the architecture of small intestinal (SI) crypts has been transformative. Here, we show that transcription factor Myb governs ISC gene expression, particularly Lgr5. Lgr5 is associated with cells that have the capacity to generate all cell lineages in SI organoid cultures and colorectal cancer cells, which overexpress Myb. Furthermore, Wnt signaling and Myb cooperate in maximal Lgr5 promoter activation while hypomorphic Myb (plt4/plt4) mice have decreased Lgr5 expression. After ionizing radiation (IR), ISC genes are elevated; but in plt4/plt4 mice, this response is substantially subdued. ISC genes bmi-1 and olfm4 are expressed at subnormal levels in plt4/plt4 mice, and bmi-1 is induced with IR to half the level in mutant mice. dcamkl-1 and olfm4 failed to recover after IR in both wild-type (wt) and mutant mice. Although not considered as an ISC gene, cyclinE1 is nevertheless used to assist cells in the emergence from a quiescent state (an expectation of ISC following IR) and is overexpressed after IR in wt mice but does not change from a very low base in plt4/plt4 mice. Self-renewal assays using organoid cultures and inducible Myb knockout studies further highlighted the dependence of ISC on Myb consistent with role in other stem cell-containing tissues. © AlphaMed Press.

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