Abstract:
The human lung is a relatively quiescent organ in the normal healthy state but contains stem/progenitor cells that contribute to normal tissue maintenance and either repair or remodeling in response to injury and disease. Maintenance or repair lead to proper restoration of functional lung tissue and maintenance of physiological functions, with remodeling resulting in altered structure and function that is typically associated with disease. Knowledge of cell types contributing to lung tissue maintenance and repair/remodeling have largely relied on mouse models of injury-repair and lineage tracing of local progenitors. Therefore, many of the functional alterations underlying remodeling in human lung disease have remained poorly defined. However, the advent of advanced genomics approaches to define the molecular phenotype of lung cells at single-cell resolution has paved the way for rapid advances in our understanding of cell types present within the normal human lung and changes that accompany disease. Here we summarize recent advances in our understanding of disease-related changes in the molecular phenotype of human lung epithelium that have emerged from single-cell transcriptomic studies. We focus attention on emerging concepts of epithelial transitional states that characterize the pathological remodeling that accompanies chronic lung diseases, including idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, cystic fibrosis, and asthma. Concepts arising from these studies are actively evolving and require corroborative studies to improve our understanding of disease mechanisms. Whenever possible, we highlight opportunities for providing a unified nomenclature in this rapidly advancing field of research. © 2022 The Pathological Society of Great Britain and Ireland.
摘要:
在正常健康状态下,人肺是相对静止的器官,但含有有助于正常组织维持以及响应于损伤和疾病的修复或重塑的干/祖细胞。维持或修复导致功能性肺组织的适当恢复和生理功能的维持,重塑导致通常与疾病相关的结构和功能改变。有助于肺组织维持和修复/重塑的细胞类型的知识在很大程度上依赖于损伤修复的小鼠模型和局部祖细胞的谱系追踪。因此,人类肺部疾病重塑的许多功能改变仍未明确。然而,以单细胞分辨率定义肺细胞分子表型的先进基因组学方法的出现,为我们对正常人肺中存在的细胞类型和伴随疾病的变化的理解的快速进展铺平了道路.在这里,我们总结了从单细胞转录组学研究中出现的人类肺上皮分子表型疾病相关变化的最新进展。我们将注意力集中在上皮过渡状态的新兴概念上,这些概念表征了伴随慢性肺部疾病的病理性重塑,包括特发性肺纤维化,慢性阻塞性肺疾病,囊性纤维化,和哮喘。这些研究产生的概念正在积极发展,需要确凿的研究来提高我们对疾病机制的理解。只要有可能,我们强调在这个快速发展的研究领域提供统一命名法的机会。©2022英国和爱尔兰病理学会。