title: Stem cells: the intestinal stem cell as a paradigm.
abstract: 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 beta-catenin, an enhancer of cell proliferation, thereby downregulating this activity in healthy individuals.
authors.affiliation: CRC Department of Epithelial Biology, Paterson Institute for Cancer Research and Department of Surgery, Christie Hospital NHS Trust, Wilmslow Road, Manchester, UK.
authors.forename: S P
authors.initials: SP
authors.lastname: Bach
authors.forename: A G
authors.initials: AG
authors.lastname: Renehan
authors.forename: C S
authors.initials: CS
authors.lastname: Potten
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D015179:Colorectal Neoplasms / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000502:physiology; D051546:Cyclooxygenase 2; D004763:Glucagon-Like Peptides; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D007422:Intestines / Q000166:cytology*; D007527:Isoenzymes / Q000235:genetics; D008565:Membrane Proteins; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*; D010455:Peptides / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D015398:Signal Transduction; D013234:Stem Cells; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D007527:Isoenzymes; D008565:Membrane Proteins; D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53; D004763:Glucagon-Like Peptides; C015236:glucagon-like-immunoreactivity; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases