npj: 皮肤白嫩无皱纹—粒子模型算得准

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生命系统的细胞增殖-死亡-增殖循环不断，组织的更替持续进行。我们的表皮每小时要损失约180万个细胞，同时在表皮-真皮界面（即基底膜）处会增生数量相当的新细胞来填补，让你的皮肤白白嫩嫩不显皱痕。

有趣的是，这个基底膜有很多微小的由真皮朝向表皮方向的突起，突起的顶端通常分布着表皮干细胞，就是由这些干细胞持续分裂填补了损失。尽管传统的屈曲理论可以很好地解释最初皮肤组织的不稳定性，但屈曲理论并不能决定这些突起的朝向，也不能决定表皮干细胞的空间分布。来自日本北海道大学的Masaharu Nagayama领导的团队，采用一种基于粒子的模型（Particle-based model）模拟了表皮更新，研究了真皮变形与真皮上表皮干细胞分布之间的关系。他们发现真皮和基底膜组成的可变形基底上，持续的细胞分裂导致基底膜拥挤。依据能量消耗，这些细胞要么从基底膜上脱离，要么使基底膜变形继续留在其中，这样便形成了真皮突起。

该模型还再现了真皮突起从真皮长向表皮的形成过程，以及表皮干细胞在真皮突起顶端的优先分布，这是基础的屈曲理论所无法解释的。他们据此认为，特定类型的细胞与基底膜之间的粘附强度，是影响这些干细胞分布的关键因素。因此，该模型也可作为其他系统分布格局形成的通用研究方法。

该文近期发表于npj Computational Materials 4: 45 (2018)  ，英文标题与摘要如下，点击左下角“阅读原文”可以自由获取论文PDF。

Interplay between epidermal stem cell dynamics and dermal deformation

Yasuaki Kobayashi, Yusuke Yasugahira, Hiroyuki Kitahata, Mika Watanabe, Ken Natsuga & Masaharu Nagayama 

Tissue growth is a driving force of morphological changes in living systems. Whereas the buckling instability is known to play a crucial role for initiating spatial pattern formations in such growing systems, little is known about the rationale for succeeding morphological changes beyond this instability. In mammalian skin, the dermis has many protrusions toward the epidermis, and the epidermal stem cells are typically found on the tips of these protrusions. Although the initial instability may well be explained by the buckling involving the dermis and the basal layer, which contains proliferative cells, it does not dictate the direction of these protrusions, nor the spatial patterning of epidermal stem cells. Here we introduce a particle-based model of self-replicating cells on a deformable substrate composed of the dermis and the basement membrane, and investigate the relationship between dermal deformation and epidermal stem cell pattering on it. We show that our model reproduces the formation of dermal protrusions directing from the dermis to the epidermis, and preferential epidermal stem cell distributions on the tips of the dermal protrusions, which the basic buckling mechanism fails to explain. We argue that cell-type-dependent adhesion strengths of the cells to the basement membrane are crucial factors influencing these patterns.

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