The Majority of Multipotent Epidermal Stem Cells Do Not Protect Their Genome by Asymmetrical Chromosome Segregation
The Majority of Multipotent Epidermal Stem Cells Do Not Protect Their Genome by Asymmetrical Chromosome Segregation
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DOI：
10.1634/stemcells.2008-0634
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发表时间：
2008-01-01
期刊：
影响因子：
5.2
通讯作者：
Blanpain, Cedric
中科院分区：
文献类型：
--
作者：
Sotiropoulou, Panagiota A.;Candi, Aurelie;Blanpain, Cedric
维持干细胞（SC）基因组完整性对于预防癌症形成和细胞衰老至关重要。永生链假说假设 SC 通过不对称细胞分裂在整个生命过程中保持相同的 DNA 链来保护其基因组，从而避免 DNA 复制过程中可能出现的突变积累。该模型的体内相关性迄今为止仍然是一个激烈争论的问题。在这项研究中，我们通过分析多能毛囊 (HF) SC 在形态发生、皮肤稳态和 SC 激活过程中如何分离其 DNA 链，重新审视了这一长期存在的假设。我们使用三种不同的体内方法来确定 HF SC 在细胞分裂过程中如何分离其 DNA 链。在形态发生和第一个成年毛发周期期间使用脉冲追踪实验进行的双标记研究表明，HF SC 包含两种不同的核苷酸类似物，这与永生链假说相矛盾。脉冲追踪实验中 DNA 和染色质标记的共分离表明，HF SC 中的标记保留是相对静止的标志。此外，与形态发生过程中的标记类似，成体 SC 的 DNA 标记也导致 HF SC 中的标记保留，表明大多数这些细胞中染色体分离是随机发生的。总而言之，我们的结果表明，在大多数 HF SC 的发育、组织稳态和 SC 激活后，DNA 链分离是随机发生的。干细胞 2008；26：2964-2973
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. STEM CELLS 2008;26:2964-2973