Most cell types are polarized with distinct structural orientations or protein localization patterns that allow cells to perform context-dependent functions in space and time in response to physiological regulation (Forte and Yao, 1996). Epithelial cell polarity is characterized by cells with apical and basolateral membrane domains, and the establishment and maintenance of cell polarity are crucial during development to specify cell fate and functions, e.g. epithelial cells undergo dynamic renewal to orchestrate the tissue homeostasis in gastrointestinal tracts for digestive physiology (Yao and Forte, 2003). However, the molecular mechanisms underlying the dynamic lineage specification and heterogenetic cell fate decision in epithelial tissues have remained elusive until the identification of leucine-rich repeat-containing, G-protein-coupled receptor 5 (Lgr5) epithelial stem cells (Sato et al., 2009). Since then, Clevers and colleagues have made paradigm shift discoveries in epithelial cell linage specification and fate determination using the mini-gut epithelial organoids comprising Lgr5⁺ stem cells and all types of differentiated lineages (Sato et al., 2009; Barker et al., 2010).

中文翻译：

---

在 4D 中模拟细胞极性、可塑性和疾病差异

米ost 细胞类型具有不同的结构取向或蛋白质定位模式，它们允许细胞响应生理调节在空间和时间中执行上下文相关的功能（Forte 和 Yao，1996）。上皮细胞极性的特征是具有顶端和基底外侧膜结构域的细胞，在发育过程中细胞极性的建立和维持对于指定细胞命运和功能至关重要，例如上皮细胞经历动态更新以协调胃肠道中的组织稳态以促进消化生理学（姚和福特，2003 年）。然而，在上皮组织中动态谱系规范和异质细胞命运决定背后的分子机制仍然难以捉摸，直到鉴定出富含亮氨酸的重复序列，G 蛋白偶联受体 5 (Lgr5) 上皮干细胞（Sato 等，2009）。从那时起，Clevers 及其同事使用包含 Lgr5 的微型肠道上皮类器官在上皮细胞谱系规范和命运决定方面取得了范式转变发现⁺干细胞和所有类型的分化谱系（Sato 等人，2009 年；Barker 等人，2010 年）。