Factor 3 regulates airway engraftment by human bronchial basal cells.

Cystic fibrosis transmembrane conductance regulator (CFTR) gene editing and transplantation of CFTR-gene corrected airway basal cells has the potential to cure CF lung disease. Although mouse studies established that cell transplantation was feasible, the engraftment rate was typically low and frequently less than the estimated therapeutic threshold. The purpose of this study was to identify genes and culture conditions that regulate the therapeutic potential of human bronchial basal cells.

Gut microbiota regulate maturation and mitochondrial function of the nutrient-sensing enteroendocrine cell.

Enteroendocrine cells (EECs) are crucial for sensing ingested nutrients and regulating feeding behavior. How gut microbiota regulate the nutrient-sensing EEC activity is unclear. Our transcriptomic analysis demonstrates that commensal microbiota colonization significantly increases the expression of many genes associated with mitochondrial function.

Gut microbiota promotes enteroendocrine cell maturation and mitochondrial function.

The enteroendocrine cells (EECs) in the intestine are crucial for sensing ingested nutrients and regulating feeding behavior. The means by which gut microbiota regulates the nutrient-sensing EEC activity is unclear. Our transcriptomic analysis of the EECs from germ-free (GF) and conventionalized (CV) zebrafish revealed that commensal microbiota colonization significantly increased the expression of many genes that are associated with mitochondrial function.

Assemblies of JAG1 and JAG2 determine tracheobronchial cell fate in mucosecretory lung disease.

Mucosecretory lung disease compromises airway epithelial function and is characterized by goblet cell hyperplasia and ciliated cell hypoplasia. Goblet and ciliated cell types are derived from tracheobronchial stem/progenitor cells via a Notch-dependent mechanism. Although specific arrays of Notch receptors regulate cell fate determination, the function of the ligands Jagged1 (JAG1) and JAG2 is unclear.

Assessment of Beta-2 Microglobulin Gene Edited Airway Epithelial Stem Cells as a treatment for Sulfur Mustard Inhalation.

Respiratory system damage is the primary cause of mortality in individuals who are exposed to vesicating agents including sulfur mustard (SM). Despite these devastating health complications, there are no fielded therapeutics that are specific for such injuries. Previous studies reported that SM inhalation depleted the tracheobronchial airway epithelial stem cell (TSC) pool and supported the hypothesis, TSC replacement will restore airway epithelial integrity and improve health outcomes for SM-exposed individuals.

Repeated injury promotes tracheobronchial tissue stem cell attrition.

Chronic lung disease has been attributed to stem cell aging and/or exhaustion. We investigated these mechanisms using mouse and human tracheobronchial tissue-specific stem cells (TSC). In mouse, chromatin labeling and flow cytometry demonstrated that naphthalene (NA) injury activated a subset of TSC.

Airway epithelial stem cell chimerism in cystic fibrosis lung transplant recipients.

Background: The conducting airway epithelium is repaired by tissue specific stem cells (TSC). In response to mild/moderate injury, each TSC repairs a discrete area of the epithelium. In contrast, severe epithelial injury stimulates TSC migration and expands the stem cell's reparative domain.

Cell Therapy for Cystic Fibrosis Lung Disease: Regenerative Basal Cell Amplification.

The human airway epithelium is regenerated by basal cells. Thus, basal cell therapy has the potential to cure cystic fibrosis (CF) lung disease. We previously reported that the human basal cells repopulated the mouse airway epithelium after transplantation, and we estimated that 60 million cells would be needed to treat a human patient.