Multi-omic comparisons between CFBE41o- cells stably expressing wild-type CFTR and F508del-mutant CFTR

Area of Science:

• Cell Biology
• Genomics
• Immunology

Background:

• Cystic Fibrosis (CF) involves lung inflammation and cytokine overproduction.
• Isogenic cell lines (CFBE for mutant F508del-CFTR, WTBE for wild-type CFTR) are crucial for CF research.
• Intrinsic cellular differences between these CF models remain largely unknown.

Purpose of the Study:

• To investigate intrinsic cellular differences between CFBE and WTBE cell lines.
• To determine the effects of wild-type CFTR expression on cell epigenome and transcriptome.
• To identify potential biomarkers for CFTR mRNA therapy.

Main Methods:

• Integrative analysis of protein, mRNA, and chromatin accessibility (ATAC-seq) in submerged and air-liquid interface (ALI) cultures.
• Comparison of cytokine secretion profiles between CFBE and WTBE cells.
• Transcriptome analysis (mRNA sequencing) to identify differentially expressed genes.

Main Results:

• CFBE and WTBE cells exhibited distinct cytokine secretion patterns (IL-6, IL-8, CXCL1, CXCL10, CCL5).
• ALI culture significantly increased cytokine secretion in both cell types.
• CFBE cells showed higher genome-wide chromatin accessibility than WTBE cells, with immune-related pathways enriched in differentially expressed genes.

Conclusions:

• Wild-type CFTR expression intrinsically affects the epithelial cell epigenome and transcriptome, particularly in immunity-related functions.
• These findings provide a valuable resource for the CF research community.
• The identified differences may serve as epithelial biomarkers for CFTR mRNA therapy.