Recent advancements in spatial transcriptomics (ST) have revolutionized our understanding of the lung’s cellular organization and pathological alterations. By preserving the spatial distribution of gene expression, ST reveals localized immune niches, stromal–epithelial interactions, and disease-associated transcriptional “hotspots” that cannot be captured by conventional sequencing methods alone. In lung cancer, ST-based investigations have delineated distinct tumor microenvironments between tumor cores and invasive fronts, revealing prognostically significant gene signatures and identifying subpopulations with differential responses to immunotherapy and chemotherapy. Similarly, in chronic obstructive pulmonary disease, asthma, and idiopathic pulmonary fibrosis, ST has mapped the ecosystem, including immune cells, inflammatory mediators, and fibroblast subtypes, of discrete regions within diseased lung tissue, offering mechanistic insights into disease progression and tissue remodeling. In addition, a more recent ST study provides spatial information for where drugs act within tissues. This review highlights the emerging role of spatial transcriptomics in respiratory research, demonstrating its potential to refine disease classification, elucidate mechanisms of therapeutic resistance, and inform spatially guided personalized interventions in respiratory diseases.
空间转录组学(ST)的最新进展彻底改变了我们对肺部细胞组织结构及病理改变的理解。该技术通过保留基因表达的空间分布,揭示了传统测序方法无法捕捉的局部免疫微环境、基质-上皮相互作用以及疾病相关转录"热点"。在肺癌研究中,基于ST的分析已明确区分肿瘤核心区与侵袭前沿的肿瘤微环境差异,揭示了具有预后意义的基因特征,并识别出对免疫治疗和化疗反应不同的细胞亚群。同样,在慢性阻塞性肺疾病、哮喘和特发性肺纤维化研究中,ST技术成功绘制了病变肺组织特定区域内免疫细胞、炎症介质及成纤维细胞亚型等要素构成的生态系统,为疾病进展和组织重塑机制提供了新见解。此外,最新ST研究还能提供药物在组织内作用部位的空间信息。本综述重点阐述空间转录组学在呼吸系统研究中的新兴作用,展示其在优化疾病分类、阐明治疗抵抗机制以及指导呼吸系统疾病空间靶向个体化干预方面的巨大潜力。
Spatial Transcriptomics in Lung Cancer and Pulmonary Diseases: A Comprehensive Review