Journal Article

Stem cells: the intestinal stem cell as a paradigm

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

in Carcinogenesis

Volume 21, issue 3, pages 469-476
Published in print March 2000 | ISSN: 0143-3334
Published online March 2000 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/21.3.469
Stem cells: the intestinal stem cell as a paradigm

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  • Clinical Cytogenetics and Molecular Genetics

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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.

Keywords: APC, adenomatous polyposis coli; DBA, Dolichos biflorus agglutinin; 3HTdR, tritiated thymidine; TGF-β, transforming growth factor β.

Journal Article.  8045 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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