2. Academic Validation
  3. Transcriptomic profiles of single-cell autophagy-related genes (ATGs) in lung diseases

Transcriptomic profiles of single-cell autophagy-related genes (ATGs) in lung diseases

  • Cell Biol Toxicol. 2025 Feb 7;41(1):40. doi: 10.1007/s10565-025-09990-w.
Xuanqi Liu # 1 2 3,  Linlin Zhang # 4,  Liyang Li # 4,  Jiayun Hou # 5,  Mengjia Qian # 5,  Nannan Zheng # 4,  Yifei Liu # 6,  Yuanlin Song 7 8 9
Affiliations

Affiliations

  • 1 Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China. 19211280001@fudan.edu.cn.
  • 2 Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University Shanghai Medical College, Shanghai, China. 19211280001@fudan.edu.cn.
  • 3 Shanghai Institute of Clinical Bioinformatics, Shanghai, China. 19211280001@fudan.edu.cn.
  • 4 Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University Shanghai Medical College, Shanghai, China.
  • 5 Shanghai Institute of Clinical Bioinformatics, Shanghai, China.
  • 6 Center of Molecular Diagnosis and Therapy, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
  • 7 Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China. song.yuanlin@zs-hospital.sh.cn.
  • 8 Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University Shanghai Medical College, Shanghai, China. song.yuanlin@zs-hospital.sh.cn.
  • 9 Shanghai Institute of Clinical Bioinformatics, Shanghai, China. song.yuanlin@zs-hospital.sh.cn.
  • # Contributed equally.
PMID: 39920481 DOI: 10.1007/s10565-025-09990-w
Abstract

Autophagy related genes (ATGs) play essential roles in maintaining cellular functions, although biological and pathological alterations of ATG phenotypes remain poorly understood. To address this knowledge gap, we utilized the single-cell Sequencing technology to elucidate the transcriptomic atlas of ATGs in lung diseases, with a focus on lung epithelium and lymphocytes. This study conducted a comprehensive investigation into RNA profiles of ATGs in the lung tissues obtained from healthy subjects and patients with different lung diseases through single-cell RNA Sequencing (scRNA-seq), including COVID-19 related acute lung damage, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), systemic sclerosis (SSC), and lung adenocarcinoma (LUAD). Our findings revealed significant variations of ATGs expression across lung epithelial cell subsets, e.g., over-expression of MAPK8 in basal cells, ATG10 in club cells, and BCL2 in a goblet cell subset. The changes of autophagy-related pathways varied between lung epithelial and lymphocyte subsets. We identified the disease-associated changes in ATG expression, including significant alterations in BCL2, BCL2L1, PRKCD, and PRKCQ in inflammatory lung diseases (COPD and IPF), and MAP2K7, MAPK3, and RHEB in lung Cancer (LUAD), as compared to normal lung tissues. Key ligand-receptor pairs (e.g., CD6-ALCAM, CD99-CD99) and signaling pathways (e.g., APP, CD74) might serve as biomarkers for lung diseases. To evaluate ATGs responses to external challenges, we examined ATGs expression in different epithelial cell lines exposed to cigarette smoking extract (CSE), lysophosphatidylcholine (lysoPC), lipopolysaccharide (LPS), and Cholesterol at various doses and durations. Notable changes were observed in CFLAR, EIF2S1, PPP2CA, and PPP2CB in A549 and H1299 against CSE and LPS. The heterogeneity of ATGs expression was dependent on cell subsets, pathologic conditions, and challenges, as well as varied among cellular phenotypes, functions, and behaviors, and the severity of lung diseases. In conclusion, our data might provide new insights into the roles of ATGs in epithelial biology and pulmonary disease pathogenesis, with implications for disease progression and prognosis.

Keywords

Autopage-related genes; epithelial cells; lymphocytes; lung disease.

Figures
Products