Kinetics of cell division in epidermal maintenance
Kinetics of cell division in epidermal maintenance
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DOI：
10.1103/physreve.76.021910
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发表时间：
2007-08-01
影响因子：
2.4
通讯作者：
Simons, Benjamin D.
中科院分区：
文献类型：
--
作者：
Klein, Allon M.;Doupe, David P.;Simons, Benjamin D.
控制细胞分裂和分化的规则对于理解发育、衰老和癌症的机制至关重要。最近的研究表明，利用可诱导的遗传标记，可以在体内追踪转基因小鼠表皮中的克隆群体。利用这些结果，我们解释了如何克隆命运的数据可能被用来推断的规则，细胞分裂和分化的成年小鼠尾部皮肤的维护。我们表明，细胞分裂和分化的速率可以通过考虑长时间和短时间的克隆命运数据进行评估，并且这些数据与细胞独立分裂而不是同步分裂是一致的。受这些发现的启发，我们认为癌症发病的机制密切基于正常成人皮肤的模型。通过分析从一个简单的两阶段突变中出现的癌症克隆命运的预期变化，我们提出克隆命运数据可能为研究疾病的最早阶段提供一种新的方法。
The rules governing cell division and differentiation are central to understanding the mechanisms of development, aging, and cancer. By utilizing inducible genetic labeling, recent studies have shown that the clonal population in transgenic mouse epidermis can be tracked in vivo. Drawing on these results, we explain how clonal fate data may be used to infer the rules of cell division and differentiation underlying the maintenance of adult murine tail-skin. We show that the rates of cell division and differentiation may be evaluated by considering the long-time and short-time clone fate data, and that the data is consistent with cells dividing independently rather than synchronously. Motivated by these findings, we consider a mechanism for cancer onset based closely on the model for normal adult skin. By analyzing the expected changes to clonal fate in cancer emerging from a simple two-stage mutation, we propose that clonal fate data may provide a novel method for studying the earliest stages of the disease.