Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection

Zou, Xin; Chen, Ke; Zou, Jiawei; Han, Peiyi; Hao, Jie; Han, Ze‐Guang

doi:10.1007/s11684-020-0754-0

Cited by 2,095 publications

(2,197 citation statements)

References 18 publications

Supporting

Mentioning

1,940

Contrasting

Unclassified

Order By: Relevance

“…1). Our results reveal that ACE2 expresses in lung AT2, liver cholangiocyte, colon colonocytes, esophagus keratinocytes, ileum ECs, rectum ECs, stomach epithelial cells, and kidney proximal tubules, consistent with the recent reports [6]. However, ACE2 expression levels are rather low in lung AT2 (4.7-fold lower than the average expression level of all ACE2 expressing cell types).…”

Section: Expression Atlas Of Ace2 Ssrna Viral Receptors and Other Mesupporting

confidence: 92%

“…As recently reported, both SARS-CoV-2 and SARS-CoV could use ACE2 protein to gain entry into the cells [4,5]. Since the outbreak, many data analysis have showed a wide distribution of ACE2 across human tissues, including lung, liver, stomach, ileum, colon and kidney [6], indicating that SARS-CoV-2 may infect multiple organs. However, these data showed that AT2 cell (the main target cell of SARS-CoV-2) in the lung actually expressed rather low levels of ACE2 [6].…”

Section: Introductionmentioning

confidence: 88%

“…Since the outbreak, many data analysis have showed a wide distribution of ACE2 across human tissues, including lung, liver, stomach, ileum, colon and kidney [6], indicating that SARS-CoV-2 may infect multiple organs. However, these data showed that AT2 cell (the main target cell of SARS-CoV-2) in the lung actually expressed rather low levels of ACE2 [6]. Hence, the SARS-CoV-2 may depends on co-receptor or other auxiliary membrane proteins to facilitate its infection.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses

Shen

Zhang

et al. 2020

Biochemical and Biophysical Research Communications

838

774

View full text Add to dashboard Cite

a b s t r a c tThe new coronavirus (SARS-CoV-2) outbreak from December 2019 in Wuhan, Hubei, China, has been declared a global public health emergency. Angiotensin I converting enzyme 2 (ACE2), is the host receptor by SARS-CoV-2 to infect human cells. Although ACE2 is reported to be expressed in lung, liver, stomach, ileum, kidney and colon, its expressing levels are rather low, especially in the lung. SARS-CoV-2 may use co-receptors/auxiliary proteins as ACE2 partner to facilitate the virus entry. To identify the potential candidates, we explored the single cell gene expression atlas including 119 cell types of 13 human tissues and analyzed the single cell co-expression spectrum of 51 reported RNA virus receptors and 400 other membrane proteins. Consistent with other recent reports, we confirmed that ACE2 was mainly expressed in lung AT2, liver cholangiocyte, colon colonocytes, esophagus keratinocytes, ileum ECs, rectum ECs, stomach epithelial cells, and kidney proximal tubules. Intriguingly, we found that the candidate co-receptors, manifesting the most similar expression patterns with ACE2 across 13 human tissues, are all peptidases, including ANPEP, DPP4 and ENPEP. Among them, ANPEP and DPP4 are the known receptors for human CoVs, suggesting ENPEP as another potential receptor for human CoVs. We also conducted "CellPhoneDB" analysis to understand the cell crosstalk between CoV-targets and their surrounding cells across different tissues. We found that macrophages frequently communicate with the CoVs targets through chemokine and phagocytosis signaling, highlighting the importance of tissue macrophages in immune defense and immune pathogenesis.

show abstract

Section: Expression Atlas Of Ace2 Ssrna Viral Receptors and Other Mesupporting

confidence: 92%

Section: Introductionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses

Shen

Zhang

et al. 2020

Biochemical and Biophysical Research Communications

838

774

View full text Add to dashboard Cite

show abstract

“…The study of Xu et al 9 found that the RBD domain of the 2019-nCoV S-protein supports strong interaction with human ACE2 molecules. These findings suggest that the ACE2 plays an important role in cellular entry, thus ACE2-expressing cells may act as target cells and are susceptible to 2019-nCoV infection 10 .…”

Section: Introductionmentioning

confidence: 83%

“…Through the developed single-cell RNA sequencing (scRNA-Seq) technique and single-cell transcriptomes based on the public database, researchers analyzed the ACE2 RNA expression profile at single-cell resolution. High ACE2 expression was identified in type II alveolar cells (AT2) of lung [10][11][12] , esophagus upper and stratified epithelial cells, absorptive enterocytes from ileum and colon 12 , cholangiocytes 13 , myocardial cells, kidney proximal tubule cells, and bladder urothelial cells 10 . These findings indicated that those organs with high ACE2-expressing cells should be considered as potential high risk for 2019-nCoV infection 10 .…”

Section: Introductionmentioning

confidence: 99%

High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa

et al. 2020

View full text Add to dashboard Cite

It has been reported that ACE2 is the main host cell receptor of 2019-nCoV and plays a crucial role in the entry of virus into the cell to cause the final infection. To investigate the potential route of 2019-nCov infection on the mucosa of oral cavity, bulk RNA-seq profiles from two public databases including The Cancer Genome Atlas (TCGA) and Functional Annotation of The Mammalian Genome Cap Analysis of Gene Expression (FANTOM5 CAGE) dataset were collected. RNA-seq profiling data of 13 organ types with para-carcinoma normal tissues from TCGA and 14 organ types with normal tissues from FANTOM5 CAGE were analyzed in order to explore and validate the expression of ACE2 on the mucosa of oral cavity. Further, single-cell transcriptomes from an independent data generated in-house were used to identify and confirm the ACE2-expressing cell composition and proportion in oral cavity. The results demonstrated that the ACE2 expressed on the mucosa of oral cavity. Interestingly, this receptor was highly enriched in epithelial cells of tongue. Preliminarily, those findings have explained the basic mechanism that the oral cavity is a potentially high risk for 2019-nCoV infectious susceptibility and provided a piece of evidence for the future prevention strategy in dental clinical practice as well as daily life.

show abstract

Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19)

Wiersinga

Rhodes

Cheng

et al. 2020

JAMA

4,443

4,322

View full text Add to dashboard Cite

IMPORTANCEThe coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19.OBSERVATIONS SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies.CONCLUSIONS AND RELEVANCE As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.

show abstract

Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection

Cited by 2,095 publications

References 18 publications

Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses

Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses

High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa

Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19)

Contact Info

Product

Resources

About