eResearch - Session 2 RNA-seq
- Roberto Barrero Gumiel
Public data
Manuscript: https://www.nature.com/articles/s41467-023-36352-z
Epithelial tissues provide front-line barriers shielding the organism from invading pathogens and harmful substances. In the airway epithelium, the combined action of multiciliated and secretory cells sustains the mucociliary escalator required for clearance of microbes and particles from the airways. Defects in mucociliary clearance or barrier integrity components are associated with recurring infections and chronic inflammation. The timely and balanced differentiation of basal cells into mature epithelial cell subsets is therefore tightly controlled. While different growth factors regulating progenitor cell proliferation have been described, little is known about the role of metabolism in these regenerative processes. Here, we show that basal cell differentiation correlates with a shift in cellular metabolism from glycolysis to fatty acid oxidation (FAO). We demonstrate both in vitro and in vivo that pharmacological and genetic impairment of FAO blocks the development of fully differentiated airway epithelial cells, compromising the repair of airway epithelia. Mechanistically, FAO links to the hexosamine biosynthesis pathway to support protein glycosylation in airway epithelial cells. Our findings unveil the metabolic network underpinning the differentiation of airway epithelia and identify novel targets for intervention to promote lung repair.
Project: PRJNA862107
Comparative gene expression profiling analysis of RNA-seq data from CD49f+NGFR+, CD49f-NGFR- cell sorted from differentiated MTEC cultures collected at ALI day 10, and MTEC culture taken at ALI t0 Overall design: Primary cells isolated from tracheas by enzymatic treatment were seeded onto 0.4 μm pore size clear polyester membrane coated with a collagen solution. At confluence, media was removed from the upper chamber to establish an air-liquid interface (ALI). Cells were collected at day 10 post air-exposure. Cultures were trypzinazed and sorted into CD49f+NGFR+ and CD49f-NGFR- subsets.
