论文标题

干细胞谱系生存是一项嘈杂的利基访问

Stem cell lineage survival as a noisy competition for niche access

论文作者

Corominas-Murtra, Bernat, Scheele, Colinda L. G. J., Kishi, Kasumi, Ellenbroek, Saskia I. J., Simons, Benjamin D., van Rheenen, Jacco, Hannezo, Edouard

论文摘要

理解干细胞电位在多大程度上是细胞中的特性,或者是来自全球组织动力学和几何形状的新兴行为,是系统和干细胞生物学的关键问题。在这里,我们提出了一种干细胞动力学的理论,是一种随机竞争,以获取空间定位的小众市场,从而产生了随机的传送带模型。细胞分裂会产生稳定的细胞流,该细胞流将细胞从小众中脱离,而随机重排使细胞可以远离生态位。重要的是,即使假设组织中的所有细胞都是分子等效的,我们也可以预测长期克隆生存概率对距离生殖位距离的距离的常见(“通用”)功能依赖性,并且仅取决于有良好的功能干细胞的出现,仅取决于随机运动的速率VS. verne驱动驱动的对流。我们测试了有关在青春期乳腺尖端,胚胎肾脏尖端以及稳态肠道隐窝的数据集上该理论的预测。重要的是,我们发现竞争的预测功能依赖性是位置的函数,因此在每个器官中的功能性干细胞数。这说明位置波动在决定干细胞数和动态方面的关键作用,我们讨论了该理论对其他环境的适用性。

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 favourably 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 on pubertal mammary gland tips, embryonic kidney tips as well homeostatic intestinal crypt. 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.

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