Tissue growth is a driving force of morphological changes in living systems. Whereas the buckling instability is known to play a crutial 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.

组织生长是生命系统形态变化的驱动力。尽管已知屈曲不稳定性在此类生长系统中对于引发空间图案形成起着至关重要的作用，但除这种不稳定性之外，对于成功进行形态学改变的基本原理知之甚少。在哺乳动物的皮肤中，真皮具有朝向表皮的许多突起，并且通常在这些突起的尖端发现表皮干细胞。尽管最初的不稳定性可以很好地解释为包含真皮和基底层的屈曲，其中包含增殖细胞，但它并不能决定这些突起的方向，也不能决定表皮干细胞的空间分布。在这里，我们介绍了一个基于粒子的自我复制细胞模型，该细胞在由真皮和基底膜组成的可变形基质上，并研究了真皮变形与表皮干细胞在其上构图之间的关系。我们表明，我们的模型再现了从真皮到表皮的真皮突起的形成，以及真皮突起尖端上的优先表皮干细胞分布，这是基本的屈曲机理无法解释的。我们认为细胞对基底膜的细胞类型依赖性粘附强度是影响这些模式的关键因素。基本的屈曲机理无法解释，并且在真皮突起的尖端具有优先的表皮干细胞分布。我们认为细胞对基底膜的细胞类型依赖性粘附强度是影响这些模式的关键因素。基本的屈曲机理无法解释，并且在真皮突起的尖端具有优先的表皮干细胞分布。我们认为细胞对基底膜的细胞类型依赖性粘附强度是影响这些模式的关键因素。