Data from: An agent-based model of anoikis in the colon crypt displays novel emergent behaviour consistent with biological observations

Colorectal cancer (CRC) is a major cause of cancer mortality. Colon crypts are multi-cellular flask-shaped invaginations of the colonic epithelium, with stem cells at their base which support the continual turnover of the epithelium with loss of cells by anoikis from the flat mucosa. Mutations in these stem cells can become embedded in the crypts, a process that is strongly implicated in CRC initiation. We describe a computational model which includes novel features, including an accurate representation of the geometry of the crypt mouth. Model simulations yield previously unseen emergent phenomena, such as localization of cell death to a small region of the crypt mouth which corresponds with that observed in vivo. A mechanism emerges in the model for regulation of crypt cellularity in response to changes in either cell proliferation rates or membrane adhesion strengths. We show that cell shape assumptions influence this behaviour, with cylinders recapitulating biology better than spheres. Potential applications of the model include determination of roles of mutations in neoplasia and exploring factors for altered crypt morphodynamics.

结直肠癌（Colorectal cancer, CRC）是癌症相关死亡的主要诱因之一。结肠隐窝是结肠上皮形成的多细胞烧瓶状内陷结构，其基底分布有干细胞，可支撑上皮持续更新，并通过平坦黏膜处的失巢凋亡（anoikis）实现细胞丢失。这类干细胞发生的突变可嵌入隐窝内，该过程与结直肠癌的起始进程密切相关。本研究构建了一款包含多项创新特性的计算模型，其中可精准复现隐窝口的几何结构。模型模拟得到了此前未被报道的涌现现象，例如细胞死亡仅局限于隐窝口的一小片区域，这与体内观测到的结果高度吻合。模型中还自发形成了可响应细胞增殖速率或膜黏附强度变化、调控隐窝细胞数量的调控机制。研究表明，细胞形状的假设前提会对该调控行为产生影响，相较于球形细胞模型，圆柱形细胞模型能更好地重现生物学特征。该模型的潜在应用场景包括探究突变在肿瘤发生（neoplasia）中的作用，以及解析影响隐窝形态动力学改变的相关因素。