tetano
Editor, Senior Moderator
Nat Med
. 2021 Mar 2.
doi: 10.1038/s41591-020-01227-z. Online ahead of print.
Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
Christoph Muus[SUP] #[/SUP][SUP] 1 2 [/SUP], Malte D Luecken[SUP] #[/SUP][SUP] 3 [/SUP], G?kcen Eraslan[SUP] #[/SUP][SUP] 4 [/SUP], Lisa Sikkema[SUP] #[/SUP][SUP] 5 [/SUP], Avinash Waghray[SUP] #[/SUP][SUP] 6 7 8 [/SUP], Graham Heimberg[SUP] #[/SUP][SUP] 4 [/SUP], Yoshihiko Kobayashi[SUP] #[/SUP][SUP] 9 [/SUP], Eeshit Dhaval Vaishnav[SUP] #[/SUP][SUP] 4 10 [/SUP], Ayshwarya Subramanian[SUP] #[/SUP][SUP] 4 [/SUP], Christopher Smillie[SUP] #[/SUP][SUP] 4 [/SUP], Karthik A Jagadeesh[SUP] #[/SUP][SUP] 4 [/SUP], Elizabeth Thu Duong[SUP] #[/SUP][SUP] 11 [/SUP], Evgenij Fiskin[SUP] #[/SUP][SUP] 4 [/SUP], Elena Torlai Triglia[SUP] #[/SUP][SUP] 4 [/SUP], Meshal Ansari[SUP] #[/SUP][SUP] 12 13 [/SUP], Peiwen Cai[SUP] #[/SUP][SUP] 14 [/SUP], Brian Lin[SUP] #[/SUP][SUP] 7 8 6 [/SUP], Justin Buchanan[SUP] #[/SUP][SUP] 15 16 [/SUP], Sijia Chen[SUP] #[/SUP][SUP] 17 [/SUP], Jian Shu[SUP] #[/SUP][SUP] 18 19 [/SUP], Adam L Haber[SUP] #[/SUP][SUP] 4 20 [/SUP], Hattie Chung[SUP] #[/SUP][SUP] 4 [/SUP], Daniel T Montoro[SUP] #[/SUP][SUP] 4 [/SUP], Taylor Adams[SUP] 21 [/SUP], Hananeh Aliee[SUP] 13 [/SUP], Samuel J Allon[SUP] 18 22 23 [/SUP], Zaneta Andrusivova[SUP] 24 [/SUP], Ilias Angelidis[SUP] 12 [/SUP], Orr Ashenberg[SUP] 4 [/SUP], Kevin Bassler[SUP] 25 [/SUP], Christophe B?cavin[SUP] 26 [/SUP], Inbal Benhar[SUP] 4 [/SUP], Joseph Bergenstr?hle[SUP] 24 [/SUP], Ludvig Bergenstr?hle[SUP] 24 [/SUP], Liam Bolt[SUP] 27 [/SUP], Emelie Braun[SUP] 28 [/SUP], Linh T Bui[SUP] 29 [/SUP], Steven Callori[SUP] 30 31 [/SUP], Mark Chaffin[SUP] 32 [/SUP], Evgeny Chichelnitskiy[SUP] 33 34 [/SUP], Joshua Chiou[SUP] 35 [/SUP], Thomas M Conlon[SUP] 12 [/SUP], Michael S Cuoco[SUP] 4 [/SUP], Anna S E Cuomo[SUP] 36 [/SUP], Marie Deprez[SUP] 26 [/SUP], Grant Duclos[SUP] 37 [/SUP], Denise Fine[SUP] 38 [/SUP], David S Fischer[SUP] 13 39 [/SUP], Shila Ghazanfar[SUP] 40 [/SUP], Astrid Gillich[SUP] 41 [/SUP], Bruno Giotti[SUP] 42 [/SUP], Joshua Gould[SUP] 4 [/SUP], Minzhe Guo[SUP] 43 [/SUP], Austin J Gutierrez[SUP] 29 [/SUP], Arun C Habermann[SUP] 44 [/SUP], Tyler Harvey[SUP] 4 [/SUP], Peng He[SUP] 27 [/SUP], Xiaomeng Hou[SUP] 45 46 [/SUP], Lijuan Hu[SUP] 28 [/SUP], Yan Hu[SUP] 47 [/SUP], Alok Jaiswal[SUP] 4 [/SUP], Lu Ji[SUP] 48 [/SUP], Peiyong Jiang[SUP] 48 [/SUP], Theodoros S Kapellos[SUP] 49 [/SUP], Christin S Kuo[SUP] 50 [/SUP], Ludvig Larsson[SUP] 51 [/SUP], Michael A Leney-Greene[SUP] 4 [/SUP], Kyungtae Lim[SUP] 52 [/SUP], Monika Litviňukov?[SUP] 53 54 [/SUP], Leif S Ludwig[SUP] 4 55 [/SUP], Soeren Lukassen[SUP] 56 57 [/SUP], Wendy Luo[SUP] 4 [/SUP], Henrike Maatz[SUP] 54 [/SUP], Elo Madissoon[SUP] 58 59 [/SUP], Lira Mamanova[SUP] 27 [/SUP], Kasidet Manakongtreecheep[SUP] 18 60 61 [/SUP], Sylvie Leroy[SUP] 62 63 [/SUP], Christoph H Mayr[SUP] 64 [/SUP], Ian M Mbano[SUP] 65 66 [/SUP], Alexi M McAdams[SUP] 67 [/SUP], Ahmad N Nabhan[SUP] 41 [/SUP], Sarah K Nyquist[SUP] 18 23 68 [/SUP], Lolita Penland[SUP] 41 [/SUP], Olivier B Poirion[SUP] 45 46 [/SUP], Sergio Poli[SUP] 21 [/SUP], CanCan Qi[SUP] 69 70 [/SUP], Rachel Queen[SUP] 71 [/SUP], Daniel Reichart[SUP] 72 73 [/SUP], Ivan Rosas[SUP] 21 [/SUP], Jonas C Schupp[SUP] 74 [/SUP], Conor V Shea[SUP] 75 [/SUP], Xingyi Shi[SUP] 75 76 [/SUP], Rahul Sinha[SUP] 77 [/SUP], Rene V Sit[SUP] 41 [/SUP], Kamil Slowikowski[SUP] 18 60 61 [/SUP], Michal Slyper[SUP] 4 [/SUP], Neal P Smith[SUP] 78 [/SUP], Alex Sountoulidis[SUP] 79 [/SUP], Maximilian Strunz[SUP] 80 [/SUP], Travis B Sullivan[SUP] 81 [/SUP], Dawei Sun[SUP] 52 [/SUP], Carlos Talavera-L?pez[SUP] 82 [/SUP], Peng Tan[SUP] 4 [/SUP], Jessica Tantivit[SUP] 18 60 61 [/SUP], Kyle J Travaglini[SUP] 41 [/SUP], Nathan R Tucker[SUP] 32 83 [/SUP], Katherine A Vernon[SUP] 18 84 [/SUP], Marc H Wadsworth[SUP] 18 23 85 [/SUP], Julia Waldman[SUP] 4 [/SUP], Xiuting Wang[SUP] 14 [/SUP], Ke Xu[SUP] 75 [/SUP], Wenjun Yan[SUP] 86 87 [/SUP], William Zhao[SUP] 14 [/SUP], Carly G K Ziegler[SUP] 18 23 88 [/SUP], NHLBI LungMap Consortium; Human Cell Atlas Lung Biological Network
Collaborators, Affiliations
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[SUP]+[/SUP]TMPRSS2[SUP]+[/SUP] 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.
. 2021 Mar 2.
doi: 10.1038/s41591-020-01227-z. Online ahead of print.
Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
Christoph Muus[SUP] #[/SUP][SUP] 1 2 [/SUP], Malte D Luecken[SUP] #[/SUP][SUP] 3 [/SUP], G?kcen Eraslan[SUP] #[/SUP][SUP] 4 [/SUP], Lisa Sikkema[SUP] #[/SUP][SUP] 5 [/SUP], Avinash Waghray[SUP] #[/SUP][SUP] 6 7 8 [/SUP], Graham Heimberg[SUP] #[/SUP][SUP] 4 [/SUP], Yoshihiko Kobayashi[SUP] #[/SUP][SUP] 9 [/SUP], Eeshit Dhaval Vaishnav[SUP] #[/SUP][SUP] 4 10 [/SUP], Ayshwarya Subramanian[SUP] #[/SUP][SUP] 4 [/SUP], Christopher Smillie[SUP] #[/SUP][SUP] 4 [/SUP], Karthik A Jagadeesh[SUP] #[/SUP][SUP] 4 [/SUP], Elizabeth Thu Duong[SUP] #[/SUP][SUP] 11 [/SUP], Evgenij Fiskin[SUP] #[/SUP][SUP] 4 [/SUP], Elena Torlai Triglia[SUP] #[/SUP][SUP] 4 [/SUP], Meshal Ansari[SUP] #[/SUP][SUP] 12 13 [/SUP], Peiwen Cai[SUP] #[/SUP][SUP] 14 [/SUP], Brian Lin[SUP] #[/SUP][SUP] 7 8 6 [/SUP], Justin Buchanan[SUP] #[/SUP][SUP] 15 16 [/SUP], Sijia Chen[SUP] #[/SUP][SUP] 17 [/SUP], Jian Shu[SUP] #[/SUP][SUP] 18 19 [/SUP], Adam L Haber[SUP] #[/SUP][SUP] 4 20 [/SUP], Hattie Chung[SUP] #[/SUP][SUP] 4 [/SUP], Daniel T Montoro[SUP] #[/SUP][SUP] 4 [/SUP], Taylor Adams[SUP] 21 [/SUP], Hananeh Aliee[SUP] 13 [/SUP], Samuel J Allon[SUP] 18 22 23 [/SUP], Zaneta Andrusivova[SUP] 24 [/SUP], Ilias Angelidis[SUP] 12 [/SUP], Orr Ashenberg[SUP] 4 [/SUP], Kevin Bassler[SUP] 25 [/SUP], Christophe B?cavin[SUP] 26 [/SUP], Inbal Benhar[SUP] 4 [/SUP], Joseph Bergenstr?hle[SUP] 24 [/SUP], Ludvig Bergenstr?hle[SUP] 24 [/SUP], Liam Bolt[SUP] 27 [/SUP], Emelie Braun[SUP] 28 [/SUP], Linh T Bui[SUP] 29 [/SUP], Steven Callori[SUP] 30 31 [/SUP], Mark Chaffin[SUP] 32 [/SUP], Evgeny Chichelnitskiy[SUP] 33 34 [/SUP], Joshua Chiou[SUP] 35 [/SUP], Thomas M Conlon[SUP] 12 [/SUP], Michael S Cuoco[SUP] 4 [/SUP], Anna S E Cuomo[SUP] 36 [/SUP], Marie Deprez[SUP] 26 [/SUP], Grant Duclos[SUP] 37 [/SUP], Denise Fine[SUP] 38 [/SUP], David S Fischer[SUP] 13 39 [/SUP], Shila Ghazanfar[SUP] 40 [/SUP], Astrid Gillich[SUP] 41 [/SUP], Bruno Giotti[SUP] 42 [/SUP], Joshua Gould[SUP] 4 [/SUP], Minzhe Guo[SUP] 43 [/SUP], Austin J Gutierrez[SUP] 29 [/SUP], Arun C Habermann[SUP] 44 [/SUP], Tyler Harvey[SUP] 4 [/SUP], Peng He[SUP] 27 [/SUP], Xiaomeng Hou[SUP] 45 46 [/SUP], Lijuan Hu[SUP] 28 [/SUP], Yan Hu[SUP] 47 [/SUP], Alok Jaiswal[SUP] 4 [/SUP], Lu Ji[SUP] 48 [/SUP], Peiyong Jiang[SUP] 48 [/SUP], Theodoros S Kapellos[SUP] 49 [/SUP], Christin S Kuo[SUP] 50 [/SUP], Ludvig Larsson[SUP] 51 [/SUP], Michael A Leney-Greene[SUP] 4 [/SUP], Kyungtae Lim[SUP] 52 [/SUP], Monika Litviňukov?[SUP] 53 54 [/SUP], Leif S Ludwig[SUP] 4 55 [/SUP], Soeren Lukassen[SUP] 56 57 [/SUP], Wendy Luo[SUP] 4 [/SUP], Henrike Maatz[SUP] 54 [/SUP], Elo Madissoon[SUP] 58 59 [/SUP], Lira Mamanova[SUP] 27 [/SUP], Kasidet Manakongtreecheep[SUP] 18 60 61 [/SUP], Sylvie Leroy[SUP] 62 63 [/SUP], Christoph H Mayr[SUP] 64 [/SUP], Ian M Mbano[SUP] 65 66 [/SUP], Alexi M McAdams[SUP] 67 [/SUP], Ahmad N Nabhan[SUP] 41 [/SUP], Sarah K Nyquist[SUP] 18 23 68 [/SUP], Lolita Penland[SUP] 41 [/SUP], Olivier B Poirion[SUP] 45 46 [/SUP], Sergio Poli[SUP] 21 [/SUP], CanCan Qi[SUP] 69 70 [/SUP], Rachel Queen[SUP] 71 [/SUP], Daniel Reichart[SUP] 72 73 [/SUP], Ivan Rosas[SUP] 21 [/SUP], Jonas C Schupp[SUP] 74 [/SUP], Conor V Shea[SUP] 75 [/SUP], Xingyi Shi[SUP] 75 76 [/SUP], Rahul Sinha[SUP] 77 [/SUP], Rene V Sit[SUP] 41 [/SUP], Kamil Slowikowski[SUP] 18 60 61 [/SUP], Michal Slyper[SUP] 4 [/SUP], Neal P Smith[SUP] 78 [/SUP], Alex Sountoulidis[SUP] 79 [/SUP], Maximilian Strunz[SUP] 80 [/SUP], Travis B Sullivan[SUP] 81 [/SUP], Dawei Sun[SUP] 52 [/SUP], Carlos Talavera-L?pez[SUP] 82 [/SUP], Peng Tan[SUP] 4 [/SUP], Jessica Tantivit[SUP] 18 60 61 [/SUP], Kyle J Travaglini[SUP] 41 [/SUP], Nathan R Tucker[SUP] 32 83 [/SUP], Katherine A Vernon[SUP] 18 84 [/SUP], Marc H Wadsworth[SUP] 18 23 85 [/SUP], Julia Waldman[SUP] 4 [/SUP], Xiuting Wang[SUP] 14 [/SUP], Ke Xu[SUP] 75 [/SUP], Wenjun Yan[SUP] 86 87 [/SUP], William Zhao[SUP] 14 [/SUP], Carly G K Ziegler[SUP] 18 23 88 [/SUP], NHLBI LungMap Consortium; Human Cell Atlas Lung Biological Network
Collaborators, Affiliations
- PMID: 33654293
- DOI: 10.1038/s41591-020-01227-z
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[SUP]+[/SUP]TMPRSS2[SUP]+[/SUP] 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.