Department of Otolaryngology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Stem Cells Dev. 2012 Jul 1;21(10):1812-21. doi: 10.1089/scd.2011.0443. Epub 2011 Dec 2.
Epithelial to mesenchymal transition (EMT) plays a critical role during normal development and in adult tissue repair. It is known that immortalized epithelial cells can undergo an EMT and become cancer stem cells, and that epithelial cells from mouse pancreatic islet and avian inner ear can acquire mesenchymal traits in vitro via EMT. However, it is unclear whether epithelial cells from mammalian sensory system can undergo an EMT and obtain features of stem/progenitor cells. In this study, we used mouse utricle sensory epithelial cells (MUCs) as a mammalian cell model to address this issue. When cultured on 2-dimensional substrates, dissociated MUCs gradually lost their columnar shape and started to expand on the substrate with downregulation of expression of epithelial junction markers and upregulation of genes and proteins that are widely shown in mesenchymal cells. Moreover, MUCs expressed genes and proteins that are usually presented in prosensory epithelial cells and stem cells. These MUCs showed potential to differentiate into epithelial cells via a reverse EMT when they were forced to suspend in culture medium. Our findings reveal that sensory epithelial cells from mammalian tissue can undergo an EMT to become cells expressing features of stem cells that can be induced to become epithelial cells via a reverse EMT. The outcomes of this study may provide a novel approach to generate epithelial progenitors for use in cell replacement therapy to treat a number of human diseases, such as hearing loss and vision loss.
上皮-间充质转化 (EMT) 在正常发育和成人组织修复中起着关键作用。已知永生上皮细胞可以经历 EMT 并成为癌症干细胞,并且来自小鼠胰腺胰岛和禽类内耳的上皮细胞可以通过 EMT 在体外获得间充质特征。然而,尚不清楚哺乳动物感觉系统的上皮细胞是否可以经历 EMT 并获得干细胞/祖细胞的特征。在这项研究中,我们使用小鼠耳石感觉上皮细胞 (MUCs) 作为哺乳动物细胞模型来解决这个问题。当在二维基质上培养时,分离的 MUCs 逐渐失去柱状形状,并开始在基质上扩展,同时下调上皮连接标记物的表达,并上调广泛存在于间充质细胞中的基因和蛋白质。此外,MUCs 表达了通常存在于前感觉上皮细胞和干细胞中的基因和蛋白质。当这些 MUCs 被迫悬浮在培养基中时,它们具有通过反向 EMT 分化为上皮细胞的潜力。我们的研究结果表明,来自哺乳动物组织的感觉上皮细胞可以经历 EMT 成为表达干细胞特征的细胞,这些细胞可以通过反向 EMT 诱导成为上皮细胞。这项研究的结果可能为利用细胞替代疗法治疗多种人类疾病(如听力损失和视力损失)产生上皮祖细胞提供一种新方法。