Single-cell RNA sequencing reveals special basal cells and fibroblasts in idiopathic pulmonary fibrosis

单细胞 RNA 测序揭示特发性肺纤维化中的特殊基底细胞和成纤维细胞

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作者:Chengji Jin #, Yahong Chen #, Yujie Wang, Jia Li, Jin Liang, Shaomao Zheng, Lipeng Zhang, Qiaoyu Li, Yongchao Wang, Fayu Ling, Yongjie Li, Yu Zheng, Qiuli Nie, Qiong Feng, Jing Wang, Huiling Yang

Abstract

Idiopathic pulmonary fibrosis (IPF) is the most predominant type of idiopathic interstitial pneumonia and has an increasing incidence, poor prognosis, and unclear pathogenesis. In order to investigate the molecular mechanisms underlying IPF further, we performed single-cell RNA sequencing analysis on three healthy controls and five IPF lung tissue samples. The results revealed a significant shift in epithelial cells (ECs) phenotypes in IPF, which may be attributed to the differentiation of alveolar type 2 cells to basal cells. In addition, several previously unrecognized basal cell subtypes were preliminarily identified, including extracellular matrix basal cells, which were increased in the IPF group. We identified a special population of fibroblasts that highly expressed extracellular matrix-related genes, POSTN, CTHRC1, COL3A1, COL5A2, and COL12A1. We propose that the close interaction between ECs and fibroblasts through ligand-receptor pairs may have a critical function in IPF development. Collectively, these outcomes provide innovative perspectives on the complexity and diversity of basal cells and fibroblasts in IPF and contribute to the understanding of possible mechanisms in pathological lung fibrosis.

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