Children's Memorial Research Center, Northwestern University, Chicago, Illinois, United States of America.
PLoS One. 2012;7(2):e31609. doi: 10.1371/journal.pone.0031609. Epub 2012 Feb 7.
The production of organ parenchyma in a rapid and reproducible manner is critical to normal development. In chimeras produced by the combination of genetically distinguishable tissues, mosaic patterns of cells derived from the combined genotypes can be visualized. These patterns comprise patches of contiguously similar genotypes and are different in different organs but similar in a given organ from individual to individual. Thus, the processes that produce the patterns are regulated and conserved. We have previously established that mosaic patches in multiple tissues are fractal, consistent with an iterative, recursive growth model with simple stereotypical division rules. Fractal dimensions of various tissues are consistent with algorithmic models in which changing a single variable (e.g. daughter cell placement after division) switches the mosaic pattern from islands to stripes of cells. Here we show that the spiral pattern previously observed in mouse cornea can also be visualized in rat chimeras. While it is generally held that the pattern is induced by stem cell division dynamics, there is an unexplained discrepancy in the speed of cellular migration and the emergence of the pattern. We demonstrate in chimeric rat corneas both island and striped patterns exist depending on the age of the animal. The patches that comprise the pattern are fractal, and the fractal dimension changes with the age of the animal and indicates the constraint in patch complexity as the spiral pattern emerges. The spiral patterns are consistent with a loxodrome. Such data are likely to be relevant to growth and cell division in organ systems and will help in understanding how organ parenchyma are generated and maintained from multipotent stem cell populations located in specific topographical locations within the organ. Ultimately, understanding algorithmic growth is likely to be essential in achieving organ regeneration in vivo or in vitro from stem cell populations.
快速且可重复地产生器官实质对于正常发育至关重要。在通过遗传上可区分的组织组合产生的嵌合体中，可以观察到源自组合基因型的细胞的镶嵌模式。这些模式由连续相似基因型的斑块组成，在不同器官中不同，但在个体之间的同一器官中相似。因此，产生这些模式的过程是受调节和保守的。我们之前已经证明，多种组织中的镶嵌斑块是分形的，与具有简单刻板分裂规则的迭代、递归生长模型一致。不同组织的分形维数与算法模型一致，在该模型中，改变单个变量（例如分裂后子细胞的位置）会将镶嵌模式从岛状转变为细胞条纹状。在这里，我们表明，以前在小鼠角膜中观察到的螺旋模式也可以在大鼠嵌合体中可视化。虽然普遍认为该模式是由干细胞分裂动力学诱导的，但细胞迁移速度和模式出现之间存在未解释的差异。我们在嵌合大鼠角膜中证明，取决于动物的年龄，既存在岛屿模式也存在条纹模式。构成图案的斑块是分形的，分形维数随动物年龄而变化，并表明随着螺旋图案的出现，斑块复杂性的限制。螺旋图案与斜航线一致。这种数据可能与器官系统中的生长和细胞分裂有关，并有助于理解多能干细胞群体位于器官特定地形位置如何产生和维持器官实质。最终，理解算法生长可能对于从干细胞群体在体内或体外实现器官再生至关重要。
