Stem cells: The intestinal stem cell as a paradigm

Andrew Renehan, Simon P. Bach, Andrew G. Renehan, Christopher S. Potten

    Research output: Contribution to journalArticlepeer-review


    Stem cell research provides a foundation for therapeutic advancement in oncology, clinical genetics and a diverse array of degenerative disorders. For example, the elucidation of pathways governing proliferative regulation and differentiation within cellular systems will result in medical strategies aimed at the root cause of cancer. At present the characterization of reliable stem cell markers is the immediate aim in this particular field. Over the past 30 years investigators have determined many of the physical and functional properties of stem cells through careful and imaginative experimentation. Intestinal stem cells reside at the crypt base and give rise to all cell types found within the crypt. They readily undergo altruistic apoptosis in response to toxic stimuli although their progeny are hardier and will regain stem cell function to repopulate the tissue compartment, giving rise to the concept of a proliferative hierarchy. Contention exists when deciding whether the full complement of cells within a crypt is derived from either a single or multiple stems. Evidence has also arisen to challenge the long held view that colorectal tumours arise from a single mutated stem cell, as early adenomas from a human XO/XY mosaic contained distinct clones. Mechanisms governing the stem cell cycle and subsequent proliferative activity largely remain obscure. The adenomatous polyposis coli gene product has, however, been shown to promote the degradation of β-catenin, an enhancer of cell proliferation, thereby downregulating this activity in healthy individuals.
    Original languageEnglish
    Pages (from-to)469-476
    Number of pages7
    Issue number3
    Publication statusPublished - 2000


    • Adenomatous Polyposis Coli/genetics
    • Animal
    • Cell Differentiation
    • Cell Division
    • Colorectal Neoplasms/pathology
    • Cyclins/physiology
    • Human
    • Intestinal Mucosa/pathology
    • Intestines/*cytology
    • Isoenzymes/genetics
    • Neoplasms/genetics/*pathology
    • Peptides/physiology
    • Prostaglandin-Endoperoxide Synthase/genetics
    • Protein p53/physiology
    • Proto-Oncogene Proteins c-bcl-2/physiology
    • Signal Transduction
    • *Stem Cells
    • Support, Non-U.S. Gov't
    • Transforming Growth Factor beta/metabolism


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