The sensory cells that are responsible for hearing include the cochlear inner hair cells (IHCs) and outer hair cells (OHCs), with the OHCs being necessary for sound sensitivity and tuning1. Both cell types are thought to arise from common progenitors; however, our understanding of the factors that control the fate of IHCs and OHCs remains limited. Here we identify Ikzf2 (which encodes Helios) as an essential transcription factor in mice that is required for OHC functional maturation and hearing. Helios is expressed in postnatal mouse OHCs, and in the cello mouse model a point mutation in Ikzf2 causes early-onset sensorineural hearing loss. Ikzf2cello/cello OHCs have greatly reduced prestin-dependent electromotile activity, a hallmark of OHC functional maturation, and show reduced levels of crucial OHC-expressed genes such as Slc26a5 (which encodes prestin) and Ocm. Moreover, we show that ectopic expression of Ikzf2 in IHCs: induces the expression of OHC-specific genes; reduces the expression of canonical IHC genes; and confers electromotility to IHCs, demonstrating that Ikzf2 can partially shift the IHC transcriptome towards an OHC-like identity.Ikzf2, which encodes the transcription factor Helios, is identified as a crucial regulator of gene expression in maturing cochlear outer hair cells, and overexpression of Ikzf2 in inner hair cells induces prestin expression and electromotility.

中文翻译：

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Helios 是外毛细胞成熟的关键转录调节因子

负责听觉的感觉细胞包括耳蜗内毛细胞 (IHC) 和外毛细胞 (OHC)，其中 OHC 是声音敏感性和调音所必需的1。这两种细胞类型都被认为起源于共同的祖细胞；然而，我们对控制 IHC 和 OHC 命运的因素的了解仍然有限。在这里，我们将 Ikzf2（编码 Helios）确定为 OHC 功能成熟和听力所需的小鼠中的重要转录因子。Helios 在出生后的小鼠 OHC 中表达，在大提琴小鼠模型中，Ikzf2 的点突变导致早发性感音神经性听力损失。Ikzf2cello/cello OHCs 大大降低了依赖于 prestin 的电动活动，这是 OHC 功能成熟的标志，并显示关键的 OHC 表达基因水平降低，例如 Slc26a5（编码 prestin）和 Ocm。此外，我们表明 Ikzf2 在 IHC 中的异位表达：诱导 OHC 特异性基因的表达；减少典型 IHC 基因的表达；并赋予 IHC 电动力，证明 Ikzf2 可以部分地将 IHC 转录组转变为类似 OHC 的身份。编码转录因子 Helios 的 Ikzf2 被确定为成熟耳蜗外毛细胞基因表达的关键调节因子，内毛细胞中的 Ikzf2 诱导 prestin 表达和电动力。