Kang Da Hyun, Kim Yoonjoo, Lee Ji Hyeon, Kang Hyeong Seok, Chung Chaeuk
Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon 34134, Republic of Korea.
Cancers (Basel). 2025 Jun 9;17(12):1912. doi: 10.3390/cancers17121912.
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和病理改变的理解。通过保留基因表达的空间分布,ST揭示了局部免疫微环境、基质-上皮相互作用以及疾病相关的转录“热点”,而这些是仅靠传统测序方法无法捕捉到的。在肺癌中,基于ST的研究已经描绘出肿瘤核心和侵袭前沿之间不同的肿瘤微环境,揭示了具有预后意义的基因特征,并识别出对免疫疗法和化疗有不同反应的亚群。同样,在慢性阻塞性肺疾病、哮喘和特发性肺纤维化中,ST已经绘制出患病肺组织内离散区域的生态系统,包括免疫细胞、炎症介质和成纤维细胞亚型,为疾病进展和组织重塑提供了机制性见解。此外,最近一项ST研究提供了药物在组织内作用位置的空间信息。本综述强调了空间转录组学在呼吸研究中的新兴作用,展示了其在完善疾病分类、阐明治疗耐药机制以及为呼吸系统疾病的空间导向个性化干预提供信息方面的潜力。