Single cell meta-analysis of EndMT and EMT state in COVID-19

被引:11
|
作者
Zhang, Lanlan [1 ,2 ]
Tang, Chuang [3 ]
Zhang, Min [4 ]
Tong, Xia [3 ,5 ]
Xie, Yingying [6 ]
Yan, Ruitong [7 ]
Wang, Xiangjun [8 ]
Zhang, Xin [3 ,5 ]
Liu, Dan [1 ,2 ]
Li, Shasha [9 ,10 ]
机构
[1] Sichuan Univ, West China Hosp, Div Pulm Dis, State Key Lab Biotherapy, Chengdu, Peoples R China
[2] Sichuan Univ, West China Hosp, Dept Resp & Crit Care Med, Chengdu, Peoples R China
[3] Sichuan Univ, West China Airport Hosp, Dept Gastroenterol, Chengdu, Peoples R China
[4] Novogene Co Ltd, Oncol Bussiness Dept, Beijing, Peoples R China
[5] Sichuan Univ, West China Hosp, Dept Gastroenterol, Chengdu, Peoples R China
[6] Sun Yat sen Univ, Affiliated Hosp 7, Dept Nephrol, Shenzhen, Peoples R China
[7] Sichuan Univ, Chengdu, Peoples R China
[8] Sun Yat Sen Univ, Affiliated Hosp 1, Guangzhou, Peoples R China
[9] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA
[10] Harvard Med Sch, Boston, MA USA
来源
FRONTIERS IN IMMUNOLOGY | 2022年 / 13卷
基金
美国国家科学基金会;
关键词
COVID-19; endothelial-mesenchymal transition (EndMT); epithelial-mesenchymal transition (EMT); single cell RNA sequencing; endothelial cells (ECs); MESENCHYMAL TRANSITION; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; MECHANISMS;
D O I
10.3389/fimmu.2022.976512
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
COVID-19 prognoses suggests that a proportion of patients develop fibrosis, but there is no evidence to indicate whether patients have progression of mesenchymal transition (MT) in the lungs. The role of MT during the COVID-19 pandemic remains poorly understood. Using single-cell RNA sequencing, we profiled the transcriptomes of cells from the lungs of healthy individuals (n = 45), COVID-19 patients (n = 58), and idiopathic pulmonary fibrosis (IPF) patients (n = 64) human lungs to map the entire MT change. This analysis enabled us to map all high-resolution matrix-producing cells and identify distinct subpopulations of endothelial cells (ECs) and epithelial cells as the primary cellular sources of MT clusters during COVID-19. For the first time, we have identied early and late subgroups of endothelial mesenchymal transition (EndMT) and epithelial-mesenchymal transition (EMT) using analysis of public databases for single-cell sequencing. We assessed epithelial subgroups by age, smoking status, and gender, and the data suggest that the proportional changes in EMT in COVID-19 are statistically significant. Further enumeration of early and late EMT suggests a correlation between invasive genes and COVID-19. Finally, EndMT is upregulated in COVID-19 patients and enriched for more inflammatory cytokines. Further, by classifying EndMT as early or late stages, we found that early EndMT was positively correlated with entry factors but this was not true for late EndMT. Exploring the MT state of may help to mitigate the fibrosis impact of SARS-CoV-2 infection.
引用
收藏
页数:12
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