Abstract
Copyright: © 2012 Mull JL, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Thirty years ago Cairns and Potten first noted that intestinal epithelial cells fail to produce carcinomas at a rate proportionate to the number of divisions they undergo throughout their lifetimes [1,2]. This observation led to the formation of the immortal DNA strand hypothesis: the suggestion that somatic stem cells segregate their DNA asymmetrically, retaining an “immortal” DNA template while passing on newly formed chromatids to daughter cells. A distinct, yet related, idea posits that somatic stem cells divide infrequently, maintaining a state of relative quiescence. In tandem, mitotic quiescence and asymmetric DNA segregation are thought to spare stem cells from accumulating mutations as they divide to replenish their respective tissues [3].
Highlights
An extension of this hypothesis holds that somatic stem cells retain thymidine analog labels due to slow division rates or asymmetric segregation of DNA [4]
Stem Cell Institute, Paul and Sheila Wellstone Muscular Dystrophy Center, and Department of Neurology, University of Minnesota Medical School, Minneapolis, Minnesota, USA
This observation led to the formation of the immortal DNA strand hypothesis: the suggestion that somatic stem cells segregate their DNA asymmetrically, retaining an “immortal” DNA template while passing on newly formed chromatids to daughter cells
Summary
An extension of this hypothesis holds that somatic stem cells retain thymidine analog labels due to slow division rates or asymmetric segregation of DNA [4]. Many researchers have employed similar strategies in an attempt to identify label-retaining cells and track asymmetric DNA distribution in a variety of tissues [6,7,8,9,10,11,12,13,14,15,16,17,18,19,20]. This controversy is due in part to ill-defined or heterogeneous stem cell populations and the complexity associated with the use of thymidine analog labeling to track DNA segregation in metazoans.
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