tetano
Editor, Senior Moderator
J Clin Invest
. 2020 Nov 12;140766.
doi: 10.1172/JCI140766. Online ahead of print.
Age-determined expression of priming protease TMPRSS2 and localization of SARS-CoV-2 in lung epithelium
Bryce A Schuler[SUP] 1 [/SUP], A Christian Habermann[SUP] 2 [/SUP], Erin J Plosa[SUP] 1 [/SUP], Chase J Taylor[SUP] 2 [/SUP], Christopher Jetter[SUP] 1 [/SUP], Nicholas M Negretti[SUP] 1 [/SUP], Meghan E Kapp[SUP] 3 [/SUP], John T Benjamin[SUP] 1 [/SUP], Peter Gulleman[SUP] 1 [/SUP], David S Nichols[SUP] 2 [/SUP], Lior Z Braunstein[SUP] 4 [/SUP], Alice Hackett[SUP] 1 [/SUP], Michael Koval[SUP] 5 [/SUP], Susan H Guttentag[SUP] 1 [/SUP], Timothy S Blackwell[SUP] 2 [/SUP], Steven A Webber[SUP] 1 [/SUP], Nicholas E Banovich[SUP] 6 [/SUP], Jonathan A Kropski[SUP] 2 [/SUP], Jennifer M S Sucre[SUP] 1 [/SUP]
Affiliations
Abstract
The SARS-CoV-2 novel coronavirus global pandemic (COVID-19) has led to millions of cases and hundreds of thousands of deaths globally. While older adults appear at high risk for severe disease, hospitalizations and deaths due to SARS-CoV-2 among children have been relatively rare. Integrating single-cell RNA sequencing (scRNA-seq) of developing mouse lung with temporally-resolved immunofluorescence in mouse and human lung tissue, we found expression of SARS-CoV-2 Spike protein primer TMPRSS2 was highest in ciliated cells and type I alveolar epithelial cells (AT1), and TMPRSS2 expression increased with aging in mice and humans. Analysis of autopsy tissue from fatal COVID-19 cases detected SARS-CoV-2 RNA most frequently in ciliated and secretory cells in airway epithelium and AT1 cells in peripheral lung. SARS-CoV-2 RNA was highly colocalized in cells expressing TMPRSS2. Together, these data demonstrate the cellular spectrum infected by SARS-CoV-2 in lung epithelium and suggest that developmental regulation of TMPRSS2 may underlie the relative protection of infants and children from severe respiratory illness.
Keywords: Expression profiling; Pulmonology.
. 2020 Nov 12;140766.
doi: 10.1172/JCI140766. Online ahead of print.
Age-determined expression of priming protease TMPRSS2 and localization of SARS-CoV-2 in lung epithelium
Bryce A Schuler[SUP] 1 [/SUP], A Christian Habermann[SUP] 2 [/SUP], Erin J Plosa[SUP] 1 [/SUP], Chase J Taylor[SUP] 2 [/SUP], Christopher Jetter[SUP] 1 [/SUP], Nicholas M Negretti[SUP] 1 [/SUP], Meghan E Kapp[SUP] 3 [/SUP], John T Benjamin[SUP] 1 [/SUP], Peter Gulleman[SUP] 1 [/SUP], David S Nichols[SUP] 2 [/SUP], Lior Z Braunstein[SUP] 4 [/SUP], Alice Hackett[SUP] 1 [/SUP], Michael Koval[SUP] 5 [/SUP], Susan H Guttentag[SUP] 1 [/SUP], Timothy S Blackwell[SUP] 2 [/SUP], Steven A Webber[SUP] 1 [/SUP], Nicholas E Banovich[SUP] 6 [/SUP], Jonathan A Kropski[SUP] 2 [/SUP], Jennifer M S Sucre[SUP] 1 [/SUP]
Affiliations
- PMID: 33180746
- DOI: 10.1172/JCI140766
Abstract
The SARS-CoV-2 novel coronavirus global pandemic (COVID-19) has led to millions of cases and hundreds of thousands of deaths globally. While older adults appear at high risk for severe disease, hospitalizations and deaths due to SARS-CoV-2 among children have been relatively rare. Integrating single-cell RNA sequencing (scRNA-seq) of developing mouse lung with temporally-resolved immunofluorescence in mouse and human lung tissue, we found expression of SARS-CoV-2 Spike protein primer TMPRSS2 was highest in ciliated cells and type I alveolar epithelial cells (AT1), and TMPRSS2 expression increased with aging in mice and humans. Analysis of autopsy tissue from fatal COVID-19 cases detected SARS-CoV-2 RNA most frequently in ciliated and secretory cells in airway epithelium and AT1 cells in peripheral lung. SARS-CoV-2 RNA was highly colocalized in cells expressing TMPRSS2. Together, these data demonstrate the cellular spectrum infected by SARS-CoV-2 in lung epithelium and suggest that developmental regulation of TMPRSS2 may underlie the relative protection of infants and children from severe respiratory illness.
Keywords: Expression profiling; Pulmonology.