Microarray Analyses of Otospheres Derived from the Cochlea in the Inner Ear Identify Putative Transcription Factors that Regulate the Characteristics of Otospheres

Stem/progenitor cells of the inner ear can be isolated as so-called otospheres from differentiated cells using a sphere forming assay. Although recent studies have demonstrated the characteristics of otospheres to some extent, most of the features of these cells are unknown. We describe the findings of transcriptome analyses with a cDNA microarray of otospheres derived from the cochleae of the inner ears of neonatal mice in order to clarify the gene expression profile of otic stem/progenitor cells. There were common transcription factors between otospheres and embryonic stem cells, which were supposed to be due to the stemness of otospheres. In comparison with the cochlear sensory epithelium, the otospheres shared characteristics with the cochlea, although several transcription factors specific for otospheres were identified. These transcription factors are expected to be essential for maintaining the characteristics of otospheres, and appear to be candidate genes that promote the direct conversion of cells into otic stem/progenitor cells. A gene expression pattern of otospheres is compared with that of the CSE and embryonic stem cells (ESCs) to clarify the unique transcriptional characteristics of otospheres as tissue-specific stem/progenitor cells.

内耳干细胞/祖细胞可通过球体形成检测法从分化细胞中分离得到，即所谓耳球（otospheres）。尽管已有近期研究在一定程度上阐明了耳球的特性，但这类细胞的绝大多数特征仍未明确。本研究针对新生小鼠内耳耳蜗来源的耳球开展cDNA微阵列（cDNA microarray）转录组分析，旨在明确内耳干细胞/祖细胞的基因表达谱。研究发现，耳球与胚胎干细胞（embryonic stem cells, ESCs）存在共有的转录因子，这一现象被认为与耳球的干细胞干性（stemness）相关。与耳蜗感觉上皮（cochlear sensory epithelium, CSE）相比，耳球与耳蜗具有部分共同特征，同时也被鉴定出多种耳球特异性转录因子。这些转录因子被认为对维持耳球的特性至关重要，同时有望成为推动细胞直接转化为内耳干细胞/祖细胞的候选基因。本研究将耳球的基因表达谱与CSE及胚胎干细胞（ESCs）进行对比，以明确耳球作为组织特异性干细胞/祖细胞所特有的转录组学特征。