The Majority of Multipotent Epidermal Stem Cells Do Not Protect Their Genome by Asymmetrical Chromosome Segregation
Article first published online: 4 SEP 2008
Copyright © 2008 AlphaMed Press
Volume 26, Issue 11, pages 2964–2973, November 2008
How to Cite
Sotiropoulou, P. A., Candi, A. and Blanpain, C. (2008), The Majority of Multipotent Epidermal Stem Cells Do Not Protect Their Genome by Asymmetrical Chromosome Segregation. STEM CELLS, 26: 2964–2973. doi: 10.1634/stemcells.2008-0634
- Issue published online: 9 JAN 2009
- Article first published online: 4 SEP 2008
- Manuscript Accepted: 23 AUG 2008
- Manuscript Received: 4 JUL 2008
- Stem cells;
- Cell division;
- Chromosome segregation;
The maintenance of genome integrity in stem cells (SCs) is critical for preventing cancer formation and cellular senescence. The immortal strand hypothesis postulates that SCs protect their genome by keeping the same DNA strand throughout life by asymmetrical cell divisions, thus avoiding accumulation of mutations that can arise during DNA replication. The in vivo relevance of this model remains to date a matter of intense debate. In this study, we revisited this long-standing hypothesis, by analyzing how multipotent hair follicle (HF) SCs segregate their DNA strands during morphogenesis, skin homeostasis, and SC activation. We used three different in vivo approaches to determine how HF SCs segregate their DNA strand during cell divisions. Double-labeling studies using pulse-chase experiments during morphogenesis and the first adult hair cycle showed that HF SCs incorporate two different nucleotide analogs, contradictory to the immortal strand hypothesis. The co-segregation of DNA and chromatin labeling during pulse-chase experiments demonstrated that label retention in HF SCs is rather a mark of relative quiescence. Moreover, DNA labeling of adult SCs, similar to labeling during morphogenesis, also resulted in label retention in HF SCs, indicating that chromosome segregation occurs randomly in most of these cells. Altogether, our results demonstrate that DNA strand segregation occurs randomly in the majority of HF SCs during development, tissue homeostasis, and following SC activation.
Disclosure of potential conflicts of interest is found at the end of this article.