小柯机器人

美国西北大学范伯格医学院Anne Duggan和Jaime García-Añoveros共同合作，近期取得一项新突破。他们研究发现Tbx2是内毛细胞与外毛细胞分化的主要调节因子。相关论文2022年5月4日在线发表于《自然》杂志上。

在没有INSM1的情况下，胚胎OHCs错误表达了一组核心IHC特异性基因，研究人员预测这些基因与IHC分化有关。

在这里，研究人员发现其中一个基因 Tbx2 是小鼠IHC与OHC分化的主要调节因子。胚胎IHC中Tbx2的消融导致它们发育为OHCs，表达早期OHC标记，如Insm1，并最终在IHC的位置发育成完全成熟的OHCs。

此外，Tbx2 对 Insm1 具有上位性：在没有这两个基因的情况下，耳蜗仅产生 OHCs，这表明TBX2是INSM1缺陷型OHCs异常转分化为IHC以及正常IHC分化所必需的。在出生后消除Tbx2，高度分化的IHCs使它们直接转分化为OHCs，将IHC特征替换为成熟而非胚胎OHCs的特征。最后，Tbx2在OHCs中的异位表达导致它们转分化为IHCs。因此，Tbx2是使IHCs与OHCs区分开来并在整个开发过程中保持这种差异的必要和充分条件。

据介绍，耳蜗使用两种类型的机械感觉细胞来探测声音。一排内毛细胞(IHCs)突触到神经元上，将感觉信息传递给大脑，三排外毛细胞(OHCs)选择性地放大听觉输入。到目前为止，有两种转录因子参与了OHCs的特异性分化，然而，据他们所知，尚未发现转录因子参与IHCs的分化。OHCs的一个转录因子INSM1在关键的胚胎期起作用，巩固OHC的命运，防止OHCs转分化为IHCs。

附：英文原文

Title: Tbx2 is a master regulator of inner versus outer hair cell differentiation

Author: Garca-Aoveros, Jaime, Clancy, John C., Foo, Chuan Zhi, Garca-Gmez, Ignacio, Zhou, Yingjie, Homma, Kazuaki, Cheatham, Mary Ann, Duggan, Anne

Issue&Volume: 2022-05-04

Abstract: The cochlea uses two types of mechanosensory cell to detect sounds. A single row of inner hair cells (IHCs) synapse onto neurons to transmit sensory information to the brain, and three rows of outer hair cells (OHCs) selectively amplify auditory inputs1. So far, two transcription factors have been implicated in the specific differentiation of OHCs, whereas, to our knowledge, none has been identified in the differentiation of IHCs2,3,4. One such transcription factor for OHCs, INSM1, acts during a crucial embryonic period to consolidate the OHC fate, preventing OHCs from transdifferentiating into IHCs2. In the absence of INSM1, embryonic OHCs misexpress a core set of IHC-specific genes, which we predict are involved in IHC differentiation. Here we find that one of these genes, Tbx2, is a master regulator of IHC versus OHC differentiation in mice. Ablation of Tbx2 in embryonic IHCs results in their development as OHCs, expressing early OHC markers such as Insm1 and eventually becoming completely mature OHCs in the position of IHCs. Furthermore, Tbx2 is epistatic to Insm1: in the absence of both genes, cochleae generate only OHCs, which suggests that TBX2 is necessary for the abnormal transdifferentiation of INSM1-deficient OHCs into IHCs, as well as for normal IHC differentiation. Ablation of Tbx2 in postnatal, largely differentiated IHCs makes them transdifferentiate directly into OHCs, replacing IHC features with those of mature and not embryonic OHCs. Finally, ectopic expression of Tbx2 in OHCs results in their transdifferentiation into IHCs. Hence, Tbx2 is both necessary and sufficient to make IHCs distinct from OHCs and maintain this difference throughout development.

DOI: 10.1038/s41586-022-04668-3

Source: https://www.nature.com/articles/s41586-022-04668-3

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