Competition for Mitogens Regulates Spermatogenic Stem Cell Homeostasis in an Open Niche
Competition for Mitogens Regulates Spermatogenic Stem Cell Homeostasis in an Open Niche
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DOI：
10.1016/j.stem.2018.11.013
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发表时间：
2019-01-03
期刊：
影响因子：
23.9
通讯作者：
Yoshida, Shosei
中科院分区：
文献类型：
--
作者：
Kitadate, Yu;Jorg, David J.;Yoshida, Shosei
在许多组织中，通过干细胞和解剖学定义的小生境之间的物理接触来维持稳态。然而，干细胞如何在细胞能动并分散在其后代中的环境中实现稳态仍然未知。以小鼠精子发生为模型，我们发现淋巴管内皮细胞提供的成纤维细胞生长因子（FGFs）对精子发生干细胞密度有着密切的调节作用。我们认为，干细胞的稳态是通过竞争有限的FGF供应来实现的。我们发现，干细胞密度对FGF剂量的定量依赖性，干细胞偏向FGF来源的定位，以及损伤后再生过程中的干细胞动力学都可以在基于“促分裂原竞争”的最小理论模型框架内预测和解释。“我们认为该模型提供了一种通用且强大的机制来支持干细胞在开放或兼性生态位环境中的稳态。
In many tissues, homeostasis is maintained by physical contact between stem cells and an anatomically defined niche. However, how stem cell homeostasis is achieved in environments where cells are motile and dispersed among their progeny remains unknown. Using murine spermatogenesis as a model, we find that spermatogenic stem cell density is tightly regulated by the supply of fibroblast growth factors (FGFs) from lymphatic endothelial cells. We propose that stem cell homeostasis is achieved through competition for a limited supply of FGFs. We show that the quantitative dependence of stem cell density on FGF dosage, the biased localization of stem cells toward FGF sources, and stem cell dynamics during regeneration following injury can all be predicted and explained within the framework of a minimal theoretical model based on "mitogen competition.'' We propose that this model provides a generic and robustmechanism to support stem cell homeostasis in open, or facultative, niche environments.