Intestinal stem cells protect their genome by selective segregation of template DNA strands - PubMed (original) (raw)

. 2002 Jun 1;115(Pt 11):2381-8.

doi: 10.1242/jcs.115.11.2381.

Affiliations

• PMID: 12006622
• DOI: 10.1242/jcs.115.11.2381

Intestinal stem cells protect their genome by selective segregation of template DNA strands

Christopher S Potten et al. J Cell Sci. 2002.

Abstract

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.

PubMed Disclaimer

Similar articles

• [Immortal DNA or epigenetic signature ?].
  Rocheteau P, Tajbakhsh S. Rocheteau P, et al. Med Sci (Paris). 2008 Oct;24(10):847-52. doi: 10.1051/medsci/20082410847. Med Sci (Paris). 2008. PMID: 18950581 Review. French.
• The immortal strand hypothesis: segregation and reconstruction.
  Rando TA. Rando TA. Cell. 2007 Jun 29;129(7):1239-43. doi: 10.1016/j.cell.2007.06.019. Cell. 2007. PMID: 17604710 Review.
• Immortalized, pre-malignant epithelial cell populations contain long-lived, label-retaining cells that asymmetrically divide and retain their template DNA.
  Bussard KM, Boulanger CA, Kittrell FS, Behbod F, Medina D, Smith GH. Bussard KM, et al. Breast Cancer Res. 2010;12(5):R86. doi: 10.1186/bcr2754. Epub 2010 Oct 21. Breast Cancer Res. 2010. PMID: 20964820 Free PMC article.
• Intestinal epithelial stem cells do not protect their genome by asymmetric chromosome segregation.
  Escobar M, Nicolas P, Sangar F, Laurent-Chabalier S, Clair P, Joubert D, Jay P, Legraverend C. Escobar M, et al. Nat Commun. 2011 Mar 29;2:258. doi: 10.1038/ncomms1260. Nat Commun. 2011. PMID: 21448157 Free PMC article.
• High incidence of non-random template strand segregation and asymmetric fate determination in dividing stem cells and their progeny.
  Conboy MJ, Karasov AO, Rando TA. Conboy MJ, et al. PLoS Biol. 2007 May;5(5):e102. doi: 10.1371/journal.pbio.0050102. PLoS Biol. 2007. PMID: 17439301 Free PMC article.

Cited by

• Origins of cancer: ain't it just mature cells misbehaving?
  Cho CJ, Brown JW, Mills JC. Cho CJ, et al. EMBO J. 2024 Jul;43(13):2530-2551. doi: 10.1038/s44318-024-00099-0. Epub 2024 May 21. EMBO J. 2024. PMID: 38773319 Free PMC article. Review.
• Impact of enteric bacterial infections at and beyond the epithelial barrier.
  Rogers AP, Mileto SJ, Lyras D. Rogers AP, et al. Nat Rev Microbiol. 2023 Apr;21(4):260-274. doi: 10.1038/s41579-022-00794-x. Epub 2022 Sep 29. Nat Rev Microbiol. 2023. PMID: 36175770 Review.
• Clone wars: From molecules to cell competition in intestinal stem cell homeostasis and disease.
  Colozza G, Park SY, Koo BK. Colozza G, et al. Exp Mol Med. 2022 Sep;54(9):1367-1378. doi: 10.1038/s12276-022-00854-5. Epub 2022 Sep 18. Exp Mol Med. 2022. PMID: 36117218 Free PMC article. Review.
• 100 plus years of stem cell research-20 years of ISSCR.
  Lendahl U. Lendahl U. Stem Cell Reports. 2022 Jun 14;17(6):1248-1267. doi: 10.1016/j.stemcr.2022.04.004. Stem Cell Reports. 2022. PMID: 35705014 Free PMC article. Review.
• Recent advances in tissue stem cells.
  Fu X, He Q, Tao Y, Wang M, Wang W, Wang Y, Yu QC, Zhang F, Zhang X, Chen YG, Gao D, Hu P, Hui L, Wang X, Zeng YA. Fu X, et al. Sci China Life Sci. 2021 Dec;64(12):1998-2029. doi: 10.1007/s11427-021-2007-8. Epub 2021 Nov 30. Sci China Life Sci. 2021. PMID: 34865207 Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Silverchair Information Systems

• Other Literature Sources

  • The Lens - Patent Citations

• Medical

  • MedlinePlus Health Information