Intestinal stem cells protect their genome by selective segregation of template DNA strands.
Affiliation
Epithelial Biology Department, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK. potten@epistem.co.ukIssue Date
2002-06-01
Metadata
Show full item recordAbstract
The stem cells in the crypts of the small intestinal mucosa divide about a thousand times during the lifespan of a laboratory mouse, and yet they show little evidence of any decline in proliferative potential and rarely develop carcinogenic mutations, suggesting that their genome is extremely well protected. Protection against DNA-replication-induced errors can be achieved by the selective sorting of old (template) and new DNA strands with all template strands retained in the stem cell line. The template strands in the stem cells can be labelled during development or during tissue regeneration using tritiated thymidine ((3)HTdR). Labelling newly synthesised strands with a different marker (bromodeoxyuridine, BrdUrd) allows segregation of the two markers to be studied. Template strand label is retained ((3)HTdR), whereas label in the newly synthesised strands (BrdUrd) is lost following the second division of the stem cell. Random errors may occur in the template strands owing to environmental elements. These are protected against by the altruistic cell suicide (apoptosis) of the cells incurring such errors. A final level of protection for the tissue compensates for excessive deletion of stem cells via the apoptosis pathway. This is achieved by a hierarchical age structure in the stem cell compartment, with some cells being able to efficiently repair DNA damage and hence being more radioresistant. The presence of these protective mechanisms ensures that the small intestine rarely develops cancer and that stem cells can sustain the extensive cell proliferation needed during life.Citation
Intestinal stem cells protect their genome by selective segregation of template DNA strands. 2002, 115 (Pt 11):2381-8 J. Cell. Sci.Journal
Journal of Cell SciencePubMed ID
12006622Type
ArticleLanguage
enISSN
0021-9533Collections
Related articles
- [Immortal DNA or epigenetic signature ?].
- Authors: Rocheteau P, Tajbakhsh S
- Issue date: 2008 Oct
- The immortal strand hypothesis: segregation and reconstruction.
- Authors: Rando TA
- Issue date: 2007 Jun 29
- Immortalized, pre-malignant epithelial cell populations contain long-lived, label-retaining cells that asymmetrically divide and retain their template DNA.
- Authors: Bussard KM, Boulanger CA, Kittrell FS, Behbod F, Medina D, Smith GH
- Issue date: 2010
- Intestinal epithelial stem cells do not protect their genome by asymmetric chromosome segregation.
- Authors: Escobar M, Nicolas P, Sangar F, Laurent-Chabalier S, Clair P, Joubert D, Jay P, Legraverend C
- Issue date: 2011 Mar 29
- High incidence of non-random template strand segregation and asymmetric fate determination in dividing stem cells and their progeny.
- Authors: Conboy MJ, Karasov AO, Rando TA
- Issue date: 2007 May