The transcriptional landscape of the murine middle ear epithelium in vitro
The transcriptional landscape of the murine middle ear epithelium in vitro
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DOI：
10.1101/800987
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发表时间：
2019-10
期刊：
影响因子：
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通讯作者：
Apoorva Mulay;M. Chowdhury;C. James;L. Bingle;C. Bingle
中科院分区：
文献类型：
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作者：
Apoorva Mulay;M. Chowdhury;C. James;L. Bingle;C. Bingle
中耳炎（OM）是最常见的儿科疾病，并导致显着的发病率。尽管复杂的病理生理学阻碍了对潜在疾病机制的理解，但很明显，上皮异常是疾病的基础。支持OM中上皮重塑的机制仍不清楚。我们最近描述了一种新的小鼠中耳上皮细胞（mMEECs）的体外模型，其经历粘膜纤毛分化成中耳腔中所见的各种上皮细胞群。我们现在描述mMEEC在分化过程中的全基因组基因表达谱。我们比较了原始（未培养的）中耳细胞，未分化细胞的汇合培养物（ALI的第0天）和在ALI中分化7天的细胞的基因表达谱。>5000个基因在三组细胞中差异表达。大约4000个基因在原始细胞和ALI培养的第0天之间差异表达。原始细胞群显示含有混合的细胞类型，包括在培养中丢失的污染性炎症细胞。在ALI诱导的分化过程中，大约有500个基因上调。这些基因包括一些分泌基因和一些酶，但大多数与纤毛发生过程有关。我们的分化的鼠中耳上皮的体外模型表现出与中耳内所见的粘膜纤毛上皮一致的转录谱。这种上皮的转录景观的知识将提供一个基础，了解在小鼠模型OM的表型变化。
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 (day 0 of ALI) and cells that had been differentiated for 7 days at an 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. Our 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.