Gerike T G, Paulus U, Potten C S, Loeffler M
Institut für Medizinische Informatik, Statistik und Epidemiologie, Leipzig, Germany.
Cell Prolif. 1998 Apr;31(2):93-110. doi: 10.1046/j.1365-2184.1998.00113.x.
A widely accepted model of the temporal and spatial organization of proliferation and differentiation in intestinal epithelial is based on a cellular pedigree with all cells descending from a few active stem cells and undergoing a sequence of transitory divisions until the non-proliferating maturing cell stages develop. Model simulations have shown that such a pedigree concept can explain a large variety of data. However, so far there is neither a direct experimental proof for the existence of an intrinsic age structure in the transitory proliferative cell stages nor for the distinction between stem and transitory cells. It is our objective to suggest an alternative model which is based on evidence for intercellular communications such as might be mediated through gap junctions. We consider the diffusion of a hypothetical intraepithelial growth factor in a chain of cells which are connected via gap junctions. Individual cells can divide if a critical growth factor concentration is exceeded. Simulation studies show that the model is consistent with many observed features of the small intestinal crypt in steady state and after perturbation.
一种被广泛接受的肠道上皮细胞增殖和分化的时空组织模型，是基于一个细胞谱系，其中所有细胞都来自少数活跃的干细胞，并经历一系列短暂的分裂，直到非增殖性成熟细胞阶段形成。模型模拟表明，这样的谱系概念可以解释大量数据。然而，到目前为止，既没有直接的实验证据证明在短暂增殖细胞阶段存在内在年龄结构，也没有证据证明干细胞和短暂细胞之间的区别。我们的目标是提出一种替代模型，该模型基于细胞间通讯的证据，例如可能通过缝隙连接介导的通讯。我们考虑一种假设的上皮内生长因子在通过缝隙连接相连的细胞链中的扩散。如果超过临界生长因子浓度，单个细胞就可以分裂。模拟研究表明，该模型与稳态和扰动后小肠隐窝的许多观察特征一致。
