4.3 Article

The transcriptional landscape of the cultured murine middle ear epithelium in vitro

Journal

BIOLOGY OPEN
Volume 10, Issue 4, Pages -

Publisher

COMPANY BIOLOGISTS LTD
DOI: 10.1242/bio.056564

Keywords

In vitro; Middle ear; Otitis media; Transcriptomics

Categories

Funding

  1. University of Sheffield PhD Studentship
  2. MRC Harwell
  3. Biotechnology and Biological Sciences Research Council (UK) [BB/K009737/1]
  4. Action on Hearing Loss Flexi Grant
  5. Commonwealth Scholarship Commission PhD studentship [BDCS-2018-63]
  6. University of Sheffield A*STAR PhD studentship
  7. BBSRC [BB/K009737/1] Funding Source: UKRI

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The study described a novel in vitro model of mouse middle ear epithelial cells and investigated the genome wide gene expression profiles as they underwent differentiation. Significant differences were found in gene expression among different cell populations, with upregulated genes associated mainly with the process of ciliogenesis during differentiation.
Otitis media (OM) is the most common paediatric disease and leads to significant morbidity. Although understanding of underlying disease mechanisms is hampered by complex pathophysiology, it is clear that epithelial abnormalities underpin the disease. The mechanisms underpinning epithelial remodelling in OM remain unclear. We recently described a novel in vitro model of mouse middle ear epithelial cells (mMEECs) that undergoes mucociliary differentiation into the varied epithelial cell populations seen in the middle ear cavity. We now describe genome wide gene expression profiles of mMEECs as they undergo differentiation. We compared the gene expression profiles of original (uncultured) middle ear cells, confluent cultures of undifferentiated cells and cells that had been differentiated for 7 days at an air liquid interface (ALI). >5000 genes were differentially expressed among the three groups of cells. Approximately 4000 genes were differentially expressed between the original cells and day 0 of ALI culture. The original cell population was shown to contain a mix of cell types, including contaminating inflammatory cells that were lost on culture. Approximately 500 genes were upregulated during ALI induced differentiation. These included some secretory genes and some enzymes but most were associated with the process of ciliogenesis. The data suggest that the in vitro model of differentiated murine middle ear epithelium exhibits a transcriptional profile consistent with the mucociliary epithelium seen within the middle ear. Knowledge of the transcriptional landscape of this epithelium will provide a basis for understanding the phenotypic changes seen in murine models of OM.

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