Mechanism of murine epidermal maintenance:: Cell division and the voter model

Mechanism of murine epidermal maintenance:: Cell division and the voter model
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DOI:
10.1103/physreve.77.031907
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发表时间:
2008-03-01
期刊:
影响因子:
2.4
通讯作者:
Simons, Benjamin D.
Simons, Benjamin D.
中科院分区:
物理与天体物理3区
文献类型:
--
作者:
Klein, Allon M.;Doupe, David P.;Simons, Benjamin D.

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基因标记细胞群的动态可用于推断哺乳动物组织中细胞分裂的规律。最近,我们发现,在小鼠尾部皮肤中,增殖细胞被限制在二维层中,细胞根据细胞分裂的简单随机模型进行增殖和分化,仅涉及一种可以对称和不对称分裂的增殖细胞。奇怪的是,这些简单的规则提供了对细胞群动态的出色预测,而无需解决细胞的空间分布问题。然而,如果通过允许细胞随机扩散来解决细胞的空间行为,则可以推断密度波动会破坏组织汇合,这意味着细胞分裂的空间调节存在某种隐藏程度。为了推断空间调节机制,我们考虑了一个保留总体种群动态的细胞命运的二维模型。通过识别选民模型的三种变异所产生的行为,我们预测基底层中的增殖细胞应该聚集。对增殖活性染色细胞的经验相关性分析证实,预期的聚类行为确实在自然界中存在。这些发现不仅解释了细胞如何保持均匀的二维密度,还提供了生物学中选民模型统计的有趣实验示例。
The dynamics of a genetically labeled cell population may be used to infer the laws of cell division in mammalian tissue. Recently, we showed that in mouse tail skin, where proliferating cells are confined to a two-dimensional layer, cells proliferate and differentiate according to a simple stochastic model of cell division involving just one type of proliferating cell that may divide both symmetrically and asymmetrically. Curiously, these simple rules provide excellent predictions of the cell population dynamics without having to address the cells' spatial distribution. Yet, if the spatial behavior of cells is addressed by allowing cells to diffuse at random, one deduces that density fluctuations destroy tissue confluence, implying some hidden degree of spatial regulation of cell division. To infer the mechanism of spatial regulation, we consider a two-dimensional model of cell fate that preserves the overall population dynamics. By identifying the resulting behavior with a three-species variation of the voter model, we predict that proliferating cells in the basal layer should cluster. Analysis of empirical correlations of cells stained for proliferation activity confirms that the expected clustering behavior is indeed seen in nature. As well as explaining how cells maintain a uniform two-dimensional density, these findings present an interesting experimental example of voter-model statistics in biology.