CompareRhythms data in healthy and asthmatic airway epithelial cells

Rationale: Cellular circadian rhythms regulate multiple cellular processes
and have been hypothesized to influence epithelial function in asthma.
Airway resistance has circadian variability in patients with asthma,
profiling of circadian rhythms of gene expression in human airway
epithelia has not been performed. Organotypic cultures of primary human
airway epithelial cells differentiated at an air-liquid interface
recapitulate the major cell types of human airway epithelia to allow for
evaluation of gene expression not possible in vivo and demonstrate
rhythmicity of core circadian genes after temperature synchronization.
Methods:  Primary human airway epithelial cells from 6 healthy
children and 6 children with asthma were differentiated an air-liquid
interface and circadian rhythms were synchronized using cycled incubator
temperature. RNA was harvested every 4 hours and RNA-sequencing performed
to measure transcriptome-wide expression, with differential rhythmicity of
genes identified using CompareRhythms. Results: Core circadian genes ARNTL
and NR1D1 demonstrated rhythmicity in both healthy and asthmatic airway
epithelial cells with maintained phase relationships. In RNAseq data from
healthy and asthmatic airway epithelial cells, 646 (4%) of protein-coding
genes were rhythmic, with 110 genes exhibiting differential rhythmicity in
asthma. Gene set enrichment analysis using EnrichR revealed that genes in
circadian rhythm, nuclear receptor, and cell adhesion pathways were
rhythmic. Neutrophil chemotaxis, cytokine mediated signaling, and viral
protein interactions with cytokine receptor pathways demonstrated
differential (gain, loss, or change) rhythmicity in asthma. Conclusions:
Core circadian rhythm genes maintain rhythmicity in healthy and asthmatic
human airway epithelia, and regulate cytokine mediated signaling and
neutrophil chemotaxis pathways in asthmatic human airway epithelia.