2. Academic Validation
  3. A single-cell transcriptomic atlas reveals senescence and inflammation in the post-tuberculosis human lung

A single-cell transcriptomic atlas reveals senescence and inflammation in the post-tuberculosis human lung

  • Nat Microbiol. 2025 Aug;10(8):2073-2091. doi: 10.1038/s41564-025-02050-3.
Guoqiang Sun # 1 2,  Kuan Li # 3,  Jiale Ping # 4 5,  Liyun Zhao # 6,  Chao Cui # 7,  Junping Wu # 8,  Lixin Xie # 9,  Xiaojun Yao # 10,  Gang Xu # 11 12,  Shuai Ma 1 2 13,  Yanling Fan 4,  Qiaoran Wang 4 5,  Danlu Yang 14,  Bilan Luo 6,  Huiying Liu 9,  Jiayin Yang 11 12,  Weiqi Zhang 4 5 13,  Weihong Song 14,  Guoguang Zhao 15,  Xiaobing Fu 16,  Xiu-Wu Bian 17 18,  Jing Qu 19 20 21 22 23,  Si Wang 24 25,  Huaiyong Chen 26 27,  Guang-Hui Liu 28 29 30 31 32
Affiliations

Affiliations

  • 1 State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
  • 2 Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China.
  • 3 Tianjin Key Laboratory of Lung Regenerative Medicine, Haihe Hospital, Tianjin University, Tianjin, China.
  • 4 China National Center for Bioinformation, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
  • 5 University of Chinese Academy of Sciences, Beijing, China.
  • 6 Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Aging Translational Medicine Center, Beijing Municipal Geriatric Medical Research Center, Beijing Key Laboratory of Environment and Aging, Xuanwu Hospital, Capital Medical University, Beijing, China.
  • 7 Department of Thoracic Surgery, Haihe Hospital, Tianjin University, Tianjin, China.
  • 8 Department of Tuberculosis, Haihe Hospital, Tianjin University, Tianjin, China.
  • 9 College of Pulmonary and Critical Care Medicine, 8th Medical Center of Chinese PLA General Hospital, Beijing, China.
  • 10 Department of Thoracic Surgery, Public Health Clinical Center of Chengdu, Chengdu, China.
  • 11 Liver Transplant Center, Organ Transplant Center, West China Hospital of Sichuan University, Chengdu, China.
  • 12 Laboratory of Liver Transplantation, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital of Sichuan University, Chengdu, China.
  • 13 Aging Biomarker Consortium, Beijing, China.
  • 14 Oujiang Laboratory, Center for Geriatric Medicine and Institute of Aging, Key Laboratory of Alzheimer's Disease of Zhejiang Province, Zhejiang Provincial Clinical Research for Mental Disorders, The First-affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
  • 15 Department of Neurosurgery, Beijing Municipal Geriatric Medical Research Center, National Medical Center for Neurological Diseases, Xuanwu Hospital Capital Medical University, Beijing, China.
  • 16 Tissue Repair and Regeneration Research Center, Medical Innovation Department, PLA General Hospital and Medical College, Beijing, China.
  • 17 Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.
  • 18 Chongqing Institute of Advanced Pathology, Jinfeng Laboratory, Chongqing, China.
  • 19 State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. [email protected].
  • 20 Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. [email protected].
  • 21 University of Chinese Academy of Sciences, Beijing, China. [email protected].
  • 22 Aging Biomarker Consortium, Beijing, China. [email protected].
  • 23 Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. [email protected].
  • 24 Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Aging Translational Medicine Center, Beijing Municipal Geriatric Medical Research Center, Beijing Key Laboratory of Environment and Aging, Xuanwu Hospital, Capital Medical University, Beijing, China. [email protected].
  • 25 Aging Biomarker Consortium, Beijing, China. [email protected].
  • 26 Tianjin Key Laboratory of Lung Regenerative Medicine, Haihe Hospital, Tianjin University, Tianjin, China. [email protected].
  • 27 Key Research Laboratory for Infectious Disease Prevention for State Administration of Traditional Chinese Medicine, Tianjin Institute of Respiratory Diseases, Tianjin, China. [email protected].
  • 28 State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. [email protected].
  • 29 Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. [email protected].
  • 30 University of Chinese Academy of Sciences, Beijing, China. [email protected].
  • 31 Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Aging Translational Medicine Center, Beijing Municipal Geriatric Medical Research Center, Beijing Key Laboratory of Environment and Aging, Xuanwu Hospital, Capital Medical University, Beijing, China. [email protected].
  • 32 Aging Biomarker Consortium, Beijing, China. [email protected].
  • # Contributed equally.
PMID: 40659921 DOI: 10.1038/s41564-025-02050-3
Abstract

Patients with a history of Mycobacterium tuberculosis Infection often suffer from irreversible and progressive pulmonary damage, yet the underlying mechanisms are not fully understood. Here we conducted single-cell transcriptomic analysis of human lung tissues including 19 post-tuberculosis lung tissues and 13 matched normal lung samples as controls, focusing on areas within and surrounding tuberculosis lesions. We identified tuberculosis-associated molecular signatures across various cell types, including gene expression patterns associated with senescence, inflammation, fibrosis and Apoptosis. We observed increased vascular inflammation as a key feature of lung tissues following tuberculosis. Signatures of decreased FOXO3 signalling and increased NF-κB-dependent thromboinflammation were validated by showing that small interfering RNA silencing of FOXO3 and Thrombin treatment exacerbated senescence and inflammation in pulmonary endothelial cells. These findings provide insight into the mechanisms contributing to post-tuberculosis pulmonary damage and suggest potential therapeutic targets for alleviating lung impairment in these patients.

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