胃部上皮内衬经历了快速更新过程以维持其结构和功能完整性，这一过程由驻留在幽门和胃体腺中的长寿命干细胞推动。已经确定了几个不同亚群的胃干细胞，它们的表型和功能多样性与干细胞微环境的时空规范有关。我们在此回顾胃干细胞在不同位置的家庭平衡状态下的生物特征，这一特征是由报告小鼠、谱系追踪和单细胞测序所证明的。我们还回顾了胃干细胞在应对损伤时上皮再生中所扮演的角色。此外，我们还讨论了新兴证据表明，胃干细胞中癌基因驱动器的累积或干性信号通路的改变会促进胃癌的发生。鉴于微环境的基本作用，本文强调了在病理条件下重编程干细胞命运的微环境构成和信号通路在控制干细胞命运方面的作用。提出了几个未解决的问题，如干细胞的异质性和可塑性以及表观遗传调控机制与幽门螺杆菌感染引发的变态反应-癌变级联的相关性等。随着时空基因组学、转录组学和蛋白质组学的发展，以及多重筛选和追踪方法，我们预计在不久的将来将更精确地定义和表征胃干细胞及其与它们的微环境的相互作用。合理地开发和正确地转化这些发现可能带来用于上皮细胞再生和癌症治疗的新方法。©2023 Springer Nature Switzerland AG。

The epithelial lining of the stomach undergoes rapid turnover to preserve its structural and functional integrity, a process driven by long-lived stem cells residing in the antral and corpus glands. Several subpopulations of gastric stem cells have been identified and their phenotypic and functional diversities linked to spatiotemporal specification of stem cells niches. Here, we review the biological features of gastric stem cells at various locations of the stomach under homeostatic conditions, as demonstrated by reporter mice, lineage tracing, and single cell sequencing. We also review the role of gastric stem cells in epithelial regeneration in response to injury. Moreover, we discuss emerging evidence demonstrating that accumulation of oncogenic drivers or alteration of stemness signaling pathways in gastric stem cells promotes gastric cancer. Given a fundamental role of the microenvironment, this review highlights the role reprogramming of niche components and signaling pathways under pathological conditions in dictating stem cell fate. Several outstanding issues are raised, such as the relevance of stem cell heterogeneity and plasticity, and epigenetic regulatory mechanisms, to Helicobacter pylori infection-initiated metaplasia-carcinogenesis cascades. With the development of spatiotemporal genomics, transcriptomics, and proteomics, as well as multiplexed screening and tracing approaches, we anticipate that more precise definition and characterization of gastric stem cells, and the crosstalk with their niche will be delineated in the near future. Rational exploitation and proper translation of these findings may bring forward novel modalities for epithelial rejuvenation and cancer therapeutics.© 2023. Springer Nature Switzerland AG.