Journal
NATURE CELL BIOLOGY
Volume 23, Issue 12, Pages 1314-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41556-021-00796-6
Keywords
-
Categories
Funding
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA16000000]
- National Key Research and Development Program of China [2018YFC2000100, 2020YFA0804000, 2020YFA0112201, 2017YFA0103304, 2017YFA0102802, 2018YFA0107203, 2020YFA0113400]
- National Natural Science Foundation of China [81921006, 81625009, 91749202, 81861168034, 91949209, 92049304, 81822018, 82071588, 92049116, 32000510, 31900523, 32000500, 81870228, 81922027, 82125011, 82122024, 32121001, 91849132]
- COVID-19 project from Chongqing Science and Technology Commission [cstc2020jscx-fyzxX0037]
- Program of the Beijing Natural Science Foundation [Z190019, JQ20031]
- Key Research Program of the Chinese Academy of Sciences [KFZD-SW-221]
- K. C. Wong Education Foundation [GJTD-2019-06, GJTD-2019-08]
- CAS Project for Young Scientists in Basic Research [YSBR-012]
- Youth Innovation Promotion Association of CAS [E1CAZW0401, 2021078]
- Priority Union Foundation of Yunnan Provincial Science and Technology Department [202001AY070001-011]
- 14th Five-year Network Security and Informatization Plan of Chinese Academy of Sciences [WX145XQ07-18]
- State Key Laboratory of Stem Cell and Reproductive Biology
- State Key Laboratory of Membrane Biology
- Milky Way Research Foundation (MWRF)
Ask authors/readers for more resources
This study provides insights into the molecular basis of lung pathology in COVID-19 patients through multi-omics and single-nucleus transcriptomic analysis, identifying pathological features associated with SARS-CoV-2 infection such as hyperinflammation, alveolar epithelial cell exhaustion, vascular changes, and fibrosis. It also highlights lung senescence as a molecular state of COVID-19 pathology and suggests FOXO3A suppression as a potential mechanism for COVID-19 pulmonary fibrosis.
The lung is the primary organ targeted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), making respiratory failure a leading coronavirus disease 2019 (COVID-19)-related mortality. However, our cellular and molecular understanding of how SARS-CoV-2 infection drives lung pathology is limited. Here we constructed multi-omics and single-nucleus transcriptomic atlases of the lungs of patients with COVID-19, which integrate histological, transcriptomic and proteomic analyses. Our work reveals the molecular basis of pathological hallmarks associated with SARS-CoV-2 infection in different lung and infiltrating immune cell populations. We report molecular fingerprints of hyperinflammation, alveolar epithelial cell exhaustion, vascular changes and fibrosis, and identify parenchymal lung senescence as a molecular state of COVID-19 pathology. Moreover, our data suggest that FOXO3A suppression is a potential mechanism underlying the fibroblast-to-myofibroblast transition associated with COVID-19 pulmonary fibrosis. Our work depicts a comprehensive cellular and molecular atlas of the lungs of patients with COVID-19 and provides insights into SARS-CoV-2-related pulmonary injury, facilitating the identification of biomarkers and development of symptomatic treatments. Wang et al. analysed post-mortem samples of the lungs of patients with COVID-19 by bulk and single-nucleus RNA sequencing along with proteomics and discovered lung senescence as a feature of COVID-19 pathology.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available