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体外培养的小鼠中耳上皮细胞的转录景观。

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

机构信息

Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield S10 2RX, UK.

Oral and Maxillofacial Pathology, Department of Clinical Dentistry, University of Sheffield, Sheffield S10 2TA, UK.

出版信息

Biol Open. 2021 Apr 15;10(4). doi: 10.1242/bio.056564. Epub 2021 Apr 23.

Abstract

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.

摘要

中耳炎(OM)是最常见的儿科疾病,导致发病率显著增加。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,上皮异常是该病的基础。OM 中上皮重塑的机制仍不清楚。我们最近描述了一种新的体外小鼠中耳上皮细胞(mMEEC)模型,该模型经历纤毛黏液分化为中耳腔中可见的各种上皮细胞群体。我们现在描述 mMEEC 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)中耳细胞、未分化细胞的汇合培养物和在气液界面(ALI)分化 7 天的细胞的基因表达谱。三组细胞中有>5000 个基因表达差异。原始细胞群与 ALI 培养第 0 天之间有大约 4000 个基因表达差异。原始细胞群被证明含有多种细胞类型,包括培养过程中丢失的污染炎症细胞。在 ALI 诱导分化过程中有大约 500 个基因上调。其中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。数据表明,分化的小鼠中耳上皮体外模型表现出与中耳内所见的纤毛黏液上皮一致的转录谱。了解这种上皮的转录景观将为理解 OM 小鼠模型中的表型变化提供基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e2e/8084567/3257e6042af6/biolopen-10-056564-g1.jpg

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