Exploring intrinsic variability between cultured nasal and bronchial epithelia in cystic fibrosis

Lisa W. Rodenburg*, Mieke Metzemaekers, Isabelle S. van der Windt, Shannon M.A. Smits, Loes A. den Hertog-Oosterhoff, Evelien Kruisselbrink, Jesse E. Brunsveld, Sabine Michel, Karin M. de Winter-de Groot, Cornelis K. van der Ent, Ralph Stadhouders, Jeffrey M. Beekman, Gimano D. Amatngalim

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

12 Downloads (Pure)

Abstract

The nasal and bronchial epithelium are unified parts of the respiratory tract that are affected in the monogenic disorder cystic fibrosis (CF). Recent studies have uncovered that nasal and bronchial tissues exhibit intrinsic variability, including differences in mucociliary cell composition and expression of unique transcriptional regulatory proteins which relate to germ layer origin. In the present study, we explored whether intrinsic differences between nasal and bronchial epithelial cells persist in cell cultures and affect epithelial cell functioning in CF. Comparison of air–liquid interface (ALI) differentiated epithelial cells from subjects with CF revealed distinct mucociliary differentiation states of nasal and bronchial cultures. Moreover, using RNA sequencing we identified cell type-specific signature transcription factors in differentiated nasal and bronchial epithelial cells, some of which were already poised for expression in basal progenitor cells as evidenced by ATAC sequencing. Analysis of differentiated nasal and bronchial epithelial 3D organoids revealed distinct capacities for fluid secretion, which was linked to differences in ciliated cell differentiation. In conclusion, we show that unique phenotypical and functional features of nasal and bronchial epithelial cells persist in cell culture models, which can be further used to investigate the effects of tissue-specific features on upper and lower respiratory disease development in CF.

Original languageEnglish
Article number18573
JournalScientific Reports
Volume13
Issue number1
DOIs
Publication statusPublished - 30 Oct 2023

Bibliographical note

Publisher Copyright: © 2023, The Author(s).

Fingerprint

Dive into the research topics of 'Exploring intrinsic variability between cultured nasal and bronchial epithelia in cystic fibrosis'. Together they form a unique fingerprint.

Cite this