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Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS

ABSTRACT: Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS

PROVIDER: PRJNA686091 | ENA |

REPOSITORIES: ENA

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Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS

Project description:We compared differential gene expression in tracheal aspirates collected mechanically ventilated subjects with COVID-19 ARDS to gene expression in tracheal aspirates from: 1) subjects with ARDS from other casues and 2) mechanically ventilated controls without evidence of pulmonary disease.

2020-12-18 | GSE163426 | GEO

Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS.

Project description:The immunological features that distinguish COVID-19-associated acute respiratory distress syndrome (ARDS) from other causes of ARDS are incompletely understood. Here, we report the results of comparative lower respiratory tract transcriptional profiling of tracheal aspirate from 52 critically ill patients with ARDS from COVID-19 or from other etiologies, as well as controls without ARDS. In contrast to a "cytokine storm," we observe reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes. COVID-19 ARDS is characterized by a dysregulated host response with increased PTEN signaling and elevated expression of genes with non-canonical roles in inflammation and immunity. In silico analysis of gene expression identifies several candidate drugs that may modulate gene expression in COVID-19 ARDS, including dexamethasone and granulocyte colony stimulating factor. Compared to ARDS due to other types of viral pneumonia, COVID-19 is characterized by impaired interferon-stimulated gene (ISG) expression. The relationship between SARS-CoV-2 viral load and expression of ISGs is decoupled in patients with COVID-19 ARDS when compared to patients with mild COVID-19. In summary, assessment of host gene expression in the lower airways of patients reveals distinct immunological features of COVID-19 ARDS.

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mTOR Inhibition Enables Long-Term Expansion of Human Neonatal Tracheal Aspirate-Derived Airway Basal Stem Cells

Project description:Bronchopulmonary dysplasia remains one of the most common complication of prematurity, despite significant improvements in perinatal care. Functional modeling of human lung development and disease, like BPD, is limited by our ability to access the lung and to maintain relevant stem cell populations in culture. Single cell RNA-sequencing confirmed the presence of epithelial cells in tracheal aspirates obtained from intubated neonates. Using combined SMAD signaling inhibition and mTOR inhibition neonatal tracheal-aspirate derived (nTAD) basal stem cells can be expanded long-term and retain the ability to differentiate into pseudo-stratified airway epithelium. Conclusions: Our data demonstrate that neonatal tracheal aspirate-derived epithelial cells can provide a novel ex vivo human cellular model to study neonatal lung development and disease.

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mTOR Inhibition Enables Long-Term Expansion of Human Neonatal Tracheal Aspirate-Derived Airway Basal Stem Cells

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Project description:Tracheal aspirate was collected from intubated patients with SARS-CoV-2 infections or for reasons not related to COVID-19 (controls). The proteins were extracted using the MPLEx method. Proteins were digested with trypsin and analyzed by LC-MS/MS on a Thermo Q Exactive HF-X. Data was searched with MaxQuant.

2022-06-06 | MSV000089614 | MassIVE

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Project description:Pediatric patients survive from acute respiratory distress syndrome (ARDS) better than adults. However, immunological characteristics of lung tissue and peripheral circulation in pediatric ARDS has been scared. A 10-year-old girl suffered from ARDS was treated with anti-infection, anti-inflammatory regimen and with ECMO support. Air leak was fixed by surgery. Surgically dissected lung biopsies and peripheral blood cells (PBCs) were obtained from this patient and other control subjects for single cell RNA sequencing analysis. Pathological examination was also conducted on the lung biopsy. Out data revealed transcriptional characteristics of PBCs and lung microenvironment during ARDS recovery phase, and pointed out that efficient oxygen supply, appropriate immune regulation, and adequate anti-infection treatment favor for the recovery of children from ARDS.

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