特发性肺纤维化（idiopathic pulmonary fibrosis, IPF）是复杂的衰老相关疾病，前期研究提示其与多种肺组织细胞的异常相关，然而该病在病理上呈现的高度异质性严重阻碍了对其发生发展机制的深入研究。针对此问题，本项目拟应用单细胞转录组测序技术，通过比较正常和疾病状态下肺组织中的细胞类群，探明各细胞类型中的异常部分，并鉴定IPF特有的细胞类型，首次从细胞层面诠释IPF的异质性。进而深入探讨衰老机制在各细胞类型异常状态中的作用，并以经典抗衰老基因Klotho的异常为例，诠释衰老机制的细胞特异性。本项目旨在阐明IPF异质性的细胞学基础，深入认识衰老机制在IPF中的作用，对寻找IPF早期诊断及干预的新靶标具有重要的理论意义和潜在的应用价值。

Previous study implied that idiopathic pulmonary fibrosis (IPF) is a complex age-related disease involving changes in phenotypes across a variety of cell types throughout the lung. The extremely pathological heterogeneity is a major obstacle for understanding the onset and development of IPF. To tackle it, we propose to explore the pathological heterogeneity at the cellular level. To this end, we intend to perform single cell RNA sequencing of IPF and normal lung tissues to distinguish abnormal cell subpopulations of different types, and to identify rare IPF-specific cell types as well. Based on these novel findings, we plan to investigate the roles of aging mechanisms in the pathogenesis of different cell types, and reveal the cell-specific aging mechanisms through detailed characterization of dysregulation in Klotho, one of the most well-known anti-aging factors, at the single cell level. Upon the completion of this project, we hope to provide a cellular basis for clarifying the pathological heterogeneity of IPF, to give valuable insights into the roles of aging mechanism in the development of IPF, and to provide reference value and significance to the development of strategies for early diagnosis and interference in IPF.