Distinct stem/progenitor cells proliferate to regenerate the trachea, intrapulmonary airways and alveoli in COVID-19 patients

Fang, Yinshan; Liu, Helu; Huang, Huachao; Li, Haiyan; Saqi, Anjali; Li, Qiang; Que, Jianwen

doi:10.1038/s41422-020-0367-9

Cited by 65 publications

(59 citation statements)

References 13 publications

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“…Interestingly, the conserved downregulated genes were enriched for proliferating basal cell markers (46 genes) while the upregulated signature had genes(28 genes) expressed in normal basal cells (Figure 2D). A recent study reported that distinct cell populations proliferate in different regions of the respiratory system following SARS-CoV-2 infection[49].Similar cell marker enrichment trends were seen in the core SARS-CoV-2 signature (147 genes dysregulated in all the three model systems). The upregulated gene set included markers from classical monocyte (14 genes) and alveolar epithelial type 1 (15 genes) cells while the downregulated genes were enriched for proliferating basal and NK/T cell type markers.…”

supporting

confidence: 52%

Secondary analysis of transcriptomes of SARS-CoV-2 infection models to characterize COVID-19

Ghandikota

Sharma

Jegga

2020

Preprint

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Knowledge about the molecular mechanisms driving COVID-19 pathophysiology and outcomes is still limited. To learn more about COVID-19 pathophysiology we performed secondary analyses of transcriptomic data from two in vitro (Calu-3 and Vero E6 cells) and one in vivo (Ad5-hACE2-sensitized mice) models of SARS-CoV-2 infection. We found 1467 conserved differentially expressed host genes (differentially expressed in at least two of the three model system transcriptomes compared) in SARS-CoV-2 infection. To find potential genetic factors associated with COVID-19, we analyzed these conserved differentially expressed genes using known human genotype-phenotype associations. Genome-wide association study enrichment analysis showed evidence of enrichment for GWA loci associated with platelet functions, blood pressure, body mass index, respiratory functions, and neurodegenerative and neuropsychiatric diseases, among others. Since human protein complexes are known to be directly related to viral infection, we combined and analyzed the conserved transcriptomic signature with SARS-CoV-2-host protein-protein interaction data and found more than 150 gene clusters. Of these, 29 clusters (with 5 or more genes in each cluster) had at least one gene encoding protein that interacts with SARS-CoV-2 proteome. These clusters were enriched for different cell types in lung including epithelial, endothelial, and immune cell types suggesting their pathophysiological relevancy to COVID-19. Finally, pathway analysis on the conserved differentially expressed genes and gene clusters showed alterations in several pathways and biological processes that could enable in understanding or hypothesizing molecular signatures inducing pathophysiological changes, risks, or sequelae of COVID-19.

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supporting

confidence: 52%

Secondary analysis of transcriptomes of SARS-CoV-2 infection models to characterize COVID-19

Ghandikota

Sharma

Jegga

2020

Preprint

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“…Multipotent stem cells can reconstitute lung epithelium after episodes of infection or other injuries, and it was demonstrated that stem cells could proliferate in COVID-19 patients 42 . However, the expression of SARS-CoV-2 entry factors makes them potentially infectable by SARS-CoV-2, which may in turn result in a decreased capacity for lung epithelial regeneration and potentially complicate recovery from the disease.…”

Section: Discussionmentioning

confidence: 99%

Expression of SARS-CoV-2 entry factors in lung epithelial stem cells and its potential implications for COVID-19

Valyaeva

Zharikova

Kasianov

et al. 2020

Sci Rep

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SARS-CoV-2 can infiltrate the lower respiratory tract, resulting in severe respiratory failure and a high death rate. Normally, the airway and alveolar epithelium can be rapidly reconstituted by multipotent stem cells after episodes of infection. Here, we analyzed published RNA-seq datasets and demonstrated that cells of four different lung epithelial stem cell types express SARS-CoV-2 entry factors, including Ace2. Thus, stem cells can be potentially infected by SARS-CoV-2, which may lead to defects in regeneration capacity partially accounting for the severity of SARS-CoV-2 infection and its consequences.

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“…In vivo studies of SARS-CoV2-infected macaques showed viral replication in type I/II pneumocytes and in ciliated airway epithelial cells ( 157 ). In postmortem trachea and lungs of patients with COVID-19, shedding of ciliated cells into the airway lumen was observed, exposing underlying basal cells ( 43 ). These data all implicate cilia as potentially important sites of SARS-CoV1 and/or SARS-CoV2 infection.…”

Section: Viral Infectionsmentioning

confidence: 99%

First contact: the role of respiratory cilia in host-pathogen interactions in the airways

Kuek

Lee

2020

American Journal of Physiology-Lung Cellular and Molecular Phys

127

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Respiratory cilia are the driving force of the mucociliary escalator, working in conjunction with secreted airway mucus to clear inhaled debris and pathogens from the conducting airways. Respiratory cilia are also one of the first contact points between host and inhaled pathogens. Impaired ciliary function is a common pathological feature in patients with chronic airway diseases, increasing susceptibility to respiratory infections. Common respiratory pathogens including viruses, bacteria and fungi have been shown to target cilia and/or ciliated airway epithelial cells, resulting in a disruption of mucociliary clearance that may facilitate host infection. Despite being an integral component of airway innate immunity, the role of respiratory cilia and their clinical significance during airway infections is still poorly understood. This review examines the expression, structure, and function of respiratory cilia during pathogenic infection of the airways. This review also discusses specific known points of interaction of bacteria, fungi, and viruses with respiratory cilia function. The emerging biological functions of motile cilia relating to intracellular signaling and their potential immuno-regulatory roles during infection will also be discussed.

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Distinct stem/progenitor cells proliferate to regenerate the trachea, intrapulmonary airways and alveoli in COVID-19 patients

Cited by 65 publications

References 13 publications

Secondary analysis of transcriptomes of SARS-CoV-2 infection models to characterize COVID-19

Secondary analysis of transcriptomes of SARS-CoV-2 infection models to characterize COVID-19

Expression of SARS-CoV-2 entry factors in lung epithelial stem cells and its potential implications for COVID-19

First contact: the role of respiratory cilia in host-pathogen interactions in the airways

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