Development and transdifferentiation into inner hair cells require Tbx2.

Development and transdifferentiation into inner hair cells require Tbx2.
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DOI:
10.1093/nsr/nwac156
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发表时间:
2022-12
影响因子:
20.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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在哺乳动物耳蜗中,Atoh1对于外毛细胞(ohc)和内毛细胞(IHCs)的发育至关重要。虽然Ikzf2是OHC发展所必需的,但IHC发展所需的关键基因仍然未知。我们发现,新生儿IHC中Tbx2的缺失通过抑制26.7%的IHC基因和诱导56.3%的OHC基因(包括Ikzf2),导致其转分化为OHC。更重要的是,Tbx2的持续表达和Atoh1的短暂表达有效地将非感觉支持细胞重编程为表达功能性IHC标记物vGlut3的新IHC。这些新ihc的分化状况比以前报道的要先进得多。因此,Tbx2对IHC的发展至关重要,Tbx2与Atoh1在支持细胞中的共同上调代表了治疗IHC变性相关耳聋的新途径。内毛细胞是如何产生的?
Atoh1 is essential for the development of both outer hair cells (OHCs) and inner hair cells (IHCs) in the mammalian cochlea. Whereas Ikzf2 is necessary for OHC development, the key gene required for IHC development remains unknown. We found that deletion of Tbx2 in neonatal IHCs led to their transdifferentiation into OHCs by repressing 26.7% of IHC genes and inducing 56.3% of OHC genes, including Ikzf2. More importantly, persistent expression of Tbx2 coupled with transient Atoh1 expression effectively reprogrammed non-sensory supporting cells into new IHCs expressing the functional IHC marker vGlut3. The differentiation status of these new IHCs was considerably more advanced than that previously reported. Thus, Tbx2 is essential for IHC development and co-upregulation of Tbx2 with Atoh1 in supporting cells represents a new approach for treating deafness related to IHC degeneration. How to produce the inner hair cells?
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