Abstract
There are few systems which enable adult tissue stem cells to be studied. However, the gastrointestinal tract with its high degree of polarity, well-defined cell migratory pathways, and dynamic cell replacement is a model tissue providing unique opportunities for stem cell study. Lineage tracking indicates that all cell replacement originates at well-defined stem cell positions, with an associated slower cell cycle. Radiobiological studies suggest a hierarchical stem cell compartment (actual and potential stem cells). Actual stem cells have an intolerance of genotoxic damage and die via apoptosis. Stem cells also selectively sort the old and new DNA strands at division, retaining the replication error free strands in the stem cell daughter. High genotoxic sensitivity and selective sorting of old and new DNA strands, provides extremely effective protective mechanisms against both replication and random errors. This provides a new explanation for the low cancer risk in the small intestine.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bjerknes M, Cheng H (1981) The stem-cell zone of the small intestinal epithelium. III. Evidence from columnar, enteroendocrine, and mucous cells in the adult mouse. Am J Anat 160:77–91
Bjerknes M, Cheng H (2002) Multipotential stem cells in adult mouse gastric epithelium. Am J Physiol Gastrointest Liver Physiol 283:767–777
Cai W, Roberts SA, Potten CS (1997) The number of clonogenic cells in three regions of murine large intestinal crypts. Int J Rad Biol 71:573–579
Cairns J (1975) Mutation selection and the natural history of cancer. Nature 255:197–200
Cheng H (1974) Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. V. Unitarian theory of the origin of the four epithelial cell types. Am J Anat 141:537–562
Hendry JH, Potten CS, Chadwick C, Bianchi M (1982) Cell death (apoptosis) in the mouse small intestine after low doses: effects of dose-rate, 14.7 MeV neutrons, and 600 MeV (maximum energy) neutrons. Int J Radiat Biol Relat Stud Phys Chem Med 42:611–620
Ijiri K, Potten CS (1984) The reestablishment of hypersensitive cells in the crypts of irradiated mouse intestine. Int J Radiat Biol 46:609–623
Kaur P, Potten CS (1986) Circadian variation in migration velocity in small intestinal epithelium. Cell Tissue Kinet 19:591–599
Marshman E, Booth C, Potten CS (2002) The intestinal epithelial stem cell. (Our favourite cell). Bioessays 24:91–98
Meineke FA, Potten CS, Loeffler M (2001) Cell migration and organization in the intestinal crypt using a lattice-free model. Cell Prolif 34:253–266
Merok JR, Lansita JA, Tunstead JR, Sherley JL (2002) Cosegregation of chromosomes containing immortal DNA strands in cells that cycle with asymmetric stem cell kinetics. Cancer Res 162:6791–6795
Merritt AJ, Potten CS, Hickman JA, Kemp C, Balmain A, Hall P, Lane D (1994) The role of p53 in spontaneous and radiation-induced intestinal cell apoptosis in normal and p53 deficient mice. Cancer Res 54:614–617
Merritt AJ, Potten CS, Watson AJ, Loh DY, Nakayama K, Hickman JA (1995) Differential expression of bcl-2 in intestinal epithelia. Correlation with attenuation of apoptosis in colonic crypts and the incidence of colonic neoplasia. J Cell Sci 108:2261–2271
Paulus U, Potten CS, Loeffler M (1992) A model of the control of cellular regeneration in the intestinal crypt after perturbation based solely on local stem cell regulation. Cell Prolif 25:559–578
Potten CS (1977) Extreme sensitivity of some intestinal crypt cells to X and gamma irradiation. Nature 269:518–521
Potten CS (1986) Cell cycles in cell hierarchies. Int J Radiat Biol 49:257–278
Potten CS (1995) Structure, function and proliferative organisation of mammalian gut. In: Potten CS, Hendry JH (eds) Radiation and gut. Elsevier, Amsterdam, pp 1–31
Potten CS (1998) Stem cells in gastrointestinal epithelium: numbers, characteristics and death. Phil Trans Roy Soc Lond B 353:821–830
Potten CS (2004) Weiss lecture: radiation, the ideal cytotoxic agent for studying the cell biology of tissues such as the small intestine. Radiat Res 161:123–136
Potten CS, Loeffler M (1990) Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development 110:1001–1020
Potten CS, Hendry JH (1985a) Cell clones: manual of mammalian cell techniques. In: Potten CS, Hendry JH (eds) Churchill Livingstone, Edinburgh
Potten CS, Hendry JH (1985b) The microcolony assay in mouse small intestine. In: Potten CS, Hendry JH (eds) Cell clones: manual of mammalian cell techniques. Churchill Livingstone, Edinburgh, pp 50–60
Potten CS, Hume WJ, Reid P, Cairns J (1978) The segregation of DNA in epithelial stem cells. Cell: 15:899–906
Potten CS, Booth C, Pritchard DM (1997) The intestinal epithelial stem cell: the mucosal governor. Int J Exp Path 78:219–243
Potten CS, Owen G, Booth D (2002) Intestinal stem cells protect their genome by selective segregation of template DNA strands. J Cell Sci 115:2381–2388
Potten CS, Booth C, Hargreaves D (2003a) The small intestine as a model for evaluating adult tissue stem cell drug targets. Cell Proliferat 36:115–129
Potten CS, Booth C, Tudor GL, Booth D, Brady G, Hurley P, Ashton G, Clarke R, Sakakibara S, Okano H (2003b) Identification of a putative intestinal stem cell and early lineage marker: musashi-1. Differentiation 71:28–41
Smith GH (2005) Label-retaining epithelial cells in mouse mammary gland divide asymmetrically and retain their template DNA strands. Development 132:681–687
Qiu JM, Roberts SA, Potten CS (1994) Cell migration in the small and large bowel shows a strong circadian rhythm. Epithelial Cell Biol 3:137–148
Winton DJ, Ponder BA (1990) Stem-cell organization in mouse small intestine. Proc Biol Sci 241:13–18
Winton DJ, Blount MA, Ponder BA(1998) A clonal marker induced by mutation in mouse intestinal epithelium. Nature 333:463–466
Wong MH, Saam JR, Stappenbeck TS, Rexer CH, Gordon JI (2000) Genetic mosaic analysis based on Cre recombinase and navigated laser capture microdissection. Proc Natl Acad Sci U S A 97:12601–12606
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Potten, C.S., Ellis, J.R. (2006). Adult Small Intestinal Stem Cells: Identification, Location, Characteristics, and Clinical Applications. In: Morser, J., Nishikawa, S.I., Schöler, H.R. (eds) Stem Cells in Reproduction and in the Brain. Ernst Schering Research Foundation Workshop, vol 60. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-31437-7_7
Download citation
DOI: https://doi.org/10.1007/3-540-31437-7_7
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-31436-3
Online ISBN: 978-3-540-31437-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)