Understanding to what extent stem cell potential is a cell-intrinsic property or an emergent behavior coming from global tissue dynamics and geometry is a key outstanding question of systems and stem cell biology. Here, we propose a theory of stem cell dynamics as a stochastic competition for access to a spatially localized niche, giving rise to a stochastic conveyor-belt model. Cell divisions produce a steady cellular stream which advects cells away from the niche, while random rearrangements enable cells away from the niche to be favorably repositioned. Importantly, even when assuming that all cells in a tissue are molecularly equivalent, we predict a common (“universal”) functional dependence of the long-term clonal survival probability on distance from the niche, as well as the emergence of a well-defined number of functional stem cells, dependent only on the rate of random movements vs. mitosis-driven advection. We test the predictions of this theory on datasets of pubertal mammary gland tips and embryonic kidney tips, as well as homeostatic intestinal crypts. Importantly, we find good agreement for the predicted functional dependency of the competition as a function of position, and thus functional stem cell number in each organ. This argues for a key role of positional fluctuations in dictating stem cell number and dynamics, and we discuss the applicability of this theory to other settings.

了解干细胞潜力在多大程度上是细胞内在特性或来自全球组织动力学和几何形状的紧急行为是系统和干细胞生物学的一个关键突出问题。在这里，我们提出了一种干细胞动力学理论，作为进入空间局部生态位的随机竞争，从而产生了随机传送带模型。细胞分裂产生稳定的细胞流，使细胞远离生态位，而随机重排使远离生态位的细胞能够有利地重新定位。重要的是，即使假设组织中的所有细胞在分子上都是等效的，我们预测长期克隆存活概率对与生态位距离的共同（“普遍”）功能依赖性，以及明确定义的出现功能性干细胞的数量，仅取决于随机运动的速率与有丝分裂驱动的平流。我们在青春期乳腺尖端和胚胎肾尖端以及稳态肠隐窝的数据集上测试了该理论的预测。重要的是，我们发现竞争的预测功能依赖性作为位置的函数有很好的一致性，因此每个器官中的功能性干细胞数量。这证明了位置波动在决定干细胞数量和动态方面的关键作用，我们讨论了该理论在其他环境中的适用性。我们发现与预测的竞争功能依赖性作为位置函数的良好一致性，因此每个器官中的功能性干细胞数量。这证明了位置波动在决定干细胞数量和动态方面的关键作用，我们讨论了该理论在其他环境中的适用性。我们发现与预测的竞争功能依赖性作为位置函数的良好一致性，因此每个器官中的功能性干细胞数量。这证明了位置波动在决定干细胞数量和动态方面的关键作用，我们讨论了该理论在其他环境中的适用性。