Single-Cell Meta-Analysis Maps SARS-CoV-2 Entry Gene Expression Across Tissues and Demographics
A meta-analysis of 31 lung scRNA-seq studies (1.3 million cells, 228 individuals) revealed that ACE2 and TMPRSS2 co-expression increases with age and male sex in airway epithelial cells. The cell-type-specific expression patterns and associated immune pathways provide a molecular framework for understanding COVID-19 susceptibility and inform development of tissue-specific diagnostic assays.
The original study
Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics.
- Authors
- Muus C, Luecken MD, Eraslan G, Sikkema L, Waghray A, Heimberg G, et al.
- Journal
- Nature medicine
- Type
- Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
- PMID
- 33654293
Original abstract
Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.