Department of Cell and Molecular Biology, Karolinska Institutet, Solna, Sweden.
Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden.
Dev Cell. 2024 May 20;59(10):1269-1283.e6. doi: 10.1016/j.devcel.2024.03.011. Epub 2024 Apr 1.
Progenitor cells adapt their behavior in response to tissue demands. However, the molecular mechanisms controlling esophageal progenitor decisions remain largely unknown. Here, we demonstrate the presence of a Troy (Tnfrsf19)-expressing progenitor subpopulation localized to defined regions along the mouse esophageal axis. Lineage tracing and mathematical modeling demonstrate that Troy-positive progenitor cells are prone to undergoing symmetrical fate choices and contribute to esophageal tissue homeostasis long term. Functionally, TROY inhibits progenitor proliferation and enables commitment to differentiation without affecting fate symmetry. Whereas Troy expression is stable during esophageal homeostasis, progenitor cells downregulate Troy in response to tissue stress, enabling proliferative expansion of basal cells refractory to differentiation and reestablishment of tissue homeostasis. Our results demonstrate functional, spatially restricted progenitor heterogeneity in the esophageal epithelium and identify how dynamic regulation of Troy coordinates tissue generation.
祖细胞会根据组织需求调整其行为。然而，控制食管祖细胞决策的分子机制在很大程度上仍然未知。在这里，我们证明了在小鼠食管轴的特定区域存在表达 Troy（Tnfrsf19）的祖细胞亚群。谱系追踪和数学建模表明，Troy 阳性祖细胞容易进行对称命运选择，并长期有助于食管组织稳态。功能上，TROY 抑制祖细胞增殖并促进分化，而不影响命运对称性。虽然 Troy 表达在食管稳态期间是稳定的，但祖细胞在响应组织应激时下调 Troy，从而使对分化有抗性的基底细胞增殖扩张，并重新建立组织稳态。我们的结果表明食管上皮中存在功能上的、空间受限的祖细胞异质性，并确定 Troy 的动态调节如何协调组织生成。
