Repair of airway epithelia requires metabolic rewiring towards fatty acid oxidation [I]
Ontology highlight
ABSTRACT: 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
Project description:To test the role of FAO in epithelium differentiation, we assessed genome-wide transcriptional changes in Cpt1a+/- and Cpt1a-/- primary mouse tracheal epithelial cell (mTEC) cultures analysed at the end of the expansion phase (ALI day 0) or at day 5 and 7 post air-exposure by RNA-seq.
Project description:We want to observe the dynamics of MTEC differentiation by looking at the gene expression differences at two points: ALI (Air-Liquid Interface) 4 days, and ALI 7 days.
Project description:To identify genes regulating the jamming transition in healthy distal airway epithelia compared to the dysregulated state in idiopathic pulmonary fibrosis epithelia (IPF) we analyzed RNA from three (3) healthy and four (4) IPF patient cells grown at air-liquid-interface (ALI). This bulk analysis of 3 timepointes (days 4, 8, and 14 of ALI) spanning the jamming transition revealed an enrichment for ERBB- and YAP-related genes.
Project description:Much of our understanding of chromosome segregation is based on cell culture systems. Here, we examine the importance of the tissue environment for chromosome segregation by comparing chromosome segregation fidelity across several primary cell types in native and nonnative contexts. We discover that epithelial cells have increased chromosome missegregation outside of their native tissues. Using organoid culture systems, we show that tissue architecture, specifically integrin function, is required for accurate chromosome segregation. We find that tissue architecture enhances the correction of merotelic microtubule-kinetochore attachments, and this is especially important for maintaining chromosome stability in the polyploid liver. We propose that disruption of tissue architecture could underlie the widespread chromosome instability across epithelial cancers. Moreover, our findings highlight the extent to which extracellular context can influence intrinsic cellular processes and the limitations of cell culture systems for studying cells that naturally function within a tissue.