Summary/Abstract The ability to replace defective cells in an airway with cells that can engraft, integrate and restore a functional epithelium could potentially cure a number of lung diseases. Progress toward the development of strategies to regenerate the adult lung by either in vivo or ex vivo targeting of endogenous stem cells or pluripotent stem cell derivatives, is limited by our fundamental lack of understanding of the mechanisms controlling human lung development, the precise identity and function of human lung stem and progenitor cell types, and the genetic and epigenetic control of human lung fate. In this review, we intend to discuss the known stem/progenitor cell populations, their relative differences between rodents and humans, their roles in chronic lung disease, and their therapeutic prospects. Additionally, we highlight the recent breakthroughs that have increased our understanding of these cell types. These advancements include novel lineage-traced animal models and single-cell RNA sequencing of human airway cells, which have provided critical information on the stem cell subtypes, transition states, identifying cell markers, and intricate pathways that commit a stem cell to differentiate or to maintain plasticity. As our capacity to model the human lung evolves, so will our understanding of lung regeneration and our ability to target endogenous stem cells as a therapeutic approach for lung disease.

中文翻译：

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干细胞和肺再生。

总结/摘要 用能够移植、整合和恢复功能性上皮细胞的细胞替换气道中的缺陷细胞的能力可以潜在地治愈许多肺部疾病。通过体内或体外靶向内源性干细胞或多能干细胞衍生物来开发成人肺再生策略的进展受到我们对控制人肺发育的机制、精确身份和功能的根本缺乏了解的限制人肺干细胞和祖细胞类型，以及人肺命运的遗传和表观遗传控制。在这篇综述中，我们打算讨论已知的干/祖细胞群、它们在啮齿动物和人类之间的相对差异、它们在慢性肺病中的作用以及它们的治疗前景。此外，我们强调了最近的突破，这些突破增加了我们对这些细胞类型的理解。这些进步包括新的谱系追踪动物模型和人类呼吸道细胞的单细胞 RNA 测序，它们提供了关于干细胞亚型、过渡状态、识别细胞标志物以及使干细胞分化或分化的复杂途径的关键信息。保持可塑性。随着我们模拟人肺的能力不断发展，我们对肺再生的理解以及我们将内源性干细胞作为肺部疾病治疗方法的能力也将不断发展。它们提供了关于干细胞亚型、过渡状态、识别细胞标记物以及使干细胞分化或保持可塑性的复杂途径的关键信息。随着我们模拟人肺的能力不断发展，我们对肺再生的理解以及我们将内源性干细胞作为肺部疾病治疗方法的能力也将不断发展。它们提供了关于干细胞亚型、过渡状态、识别细胞标记物以及使干细胞分化或保持可塑性的复杂途径的关键信息。随着我们模拟人肺的能力不断发展，我们对肺再生的理解以及我们将内源性干细胞作为肺部疾病治疗方法的能力也将不断发展。