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Updated: Oct 3, 2025
Generation of Human Nasal Epithelial Cell Spheroids for Individualized Cystic Fibrosis Transmembrane Conductance Regulator Study
Published on: April 11, 2018
Expression of cystic fibrosis lung disease modifier genes in human airway models
Gengming He1, Naim Panjwani2, Julie Avolio3
1Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; Program in Genetics and Genome Biology, the Hospital for Sick Children, Toronto, Ontario, Canada.
Background:
Variation in respiratory response to cystic fibrosis (CF) small molecule therapies is due in part to the contribution of CF lung disease modifier genes. Cultured human bronchial epithelia (HBE) is the gold standard respiratory model for assessing CF therapeutic efficacy but it is hard to access. Cultured human nasal epithelia (HNE) is proposed as a more accessible surrogate model but it is unknown whether the expression profile of the modifier genes are comparable between HNE and HBE which we assess here.
Methods:
RNA-sequencing was conducted on paired cultured and fresh HNE and HBE (n = 71 samples) collected from 21 individuals with CF. Genome-wide gene expression was first compared between cultured and fresh cells and then between cultured HNE and HBE based on an equivalence testing procedure we implemented. The co-expression relationships of CFTR and CF lung disease modifier genes were compared between cultured HNE and HBE to determine equivalent interactions.
Results:
The culturing process had little impact on the expression level of CF lung disease modifier genes. Over 90% of expressed genes showed significant equivalent expression level across cultured HNE and HBE (expression fold-change<2, FDR<0.1), including CFTR and CF lung disease modifier genes. The difference in co-expression relationships among these genes was not significant (p-value=0.99), suggesting their functional interactions are likely to be consistent in the two models.
Conclusions:
Cultured HNE recapitulates the expression profile of CF lung disease modifier genes in cultured HBE, suggesting the biological processes involving these genes are likely to be consistent across the two models.
Insights
Cultured human nasal epithelia (HNE) effectively mirrors the gene expression of cultured human bronchial epithelia (HBE) in cystic fibrosis (CF) research. This validates HNE as a viable alternative model for studying CF lung disease modifier genes and therapeutic responses.
Area of Science:
- Pulmonary Medicine
- Genetics
- Cell Biology
Background:
- Therapeutic responses to cystic fibrosis (CF) small molecule treatments vary due to CF lung disease modifier genes.
- Cultured human bronchial epithelia (HBE) is the standard model for CF drug efficacy but is difficult to obtain.
- Cultured human nasal epithelia (HNE) offers a more accessible alternative, but its comparability to HBE for modifier gene expression was previously unevaluated.
Purpose of the Study:
- To assess the comparability of gene expression profiles between cultured human nasal epithelia (HNE) and cultured human bronchial epithelia (HBE).
- To determine if HNE can serve as a reliable surrogate model for studying CF lung disease modifier genes.
- To evaluate the equivalence of CFTR and modifier gene co-expression patterns in HNE versus HBE.
Main Methods:
- RNA-sequencing was performed on 71 paired fresh and cultured HNE and HBE samples from 21 CF patients.
- Genome-wide gene expression was compared between fresh and cultured cells, and between HNE and HBE using equivalence testing.
- Co-expression relationships of CFTR and CF lung disease modifier genes were analyzed to assess functional consistency.
Main Results:
- The culturing process minimally impacted CF lung disease modifier gene expression.
- Over 90% of genes, including CFTR and modifier genes, exhibited equivalent expression levels between cultured HNE and HBE (fold-change < 2, FDR < 0.1).
- No significant differences were observed in the co-expression relationships of these genes (p=0.99), indicating consistent functional interactions.
Conclusions:
- Cultured HNE accurately reflects the gene expression profile of cultured HBE concerning CF lung disease modifier genes.
- The findings support the use of cultured HNE as a comparable and more accessible model for CF research.
- Biological processes involving CF lung disease modifier genes are likely consistent between HNE and HBE models.
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