Sox8 remodels the cranial ectoderm to generate the ear.
Sox8 remodels the cranial ectoderm to generate the ear.
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Sox8重塑颅外胚层，形成耳朵。
DOI：
10.1073/pnas.2118938119
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发表时间：
2022-07-12
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
内耳负责听觉和平衡感，对于与环境的沟通至关重要。在人类中，耳朵的发育畸形具有终身的后果，而与年龄相关的听力缺陷影响了很大一部分人口。然而，许多潜在的遗传机制仍然未知，也没有再生策略。在这里，我们的特点转录和监管景观的穗祖细胞，提供前所未有的细节，早期穗发育的分子方面。我们确定转录因子Sox 8作为启动耳程序，包括耳神经发生的关键调节器。我们的研究结果不仅阐明了细胞命运决定在胚胎中是如何调节的，而且还可以为耳朵的重编程和再生策略提供信息。脊椎动物的内耳起源于一群祖细胞，这些祖细胞有可能促进头部的所有感觉器官和颅神经节。在这里，我们探讨了从这些前体控制耳朵规格的分子机制。使用多组学方法结合功能丧失实验，我们确定了一个核心的转录电路，赋予耳朵的身份，沿着全基因组的非编码元件，整合这些信息的表征。该分析将转录因子Sox 8置于穗决定网络的顶部。将Sox 8引入颅外胚层不仅将非耳细胞转化为耳祖细胞，而且还激活了耳形态发生和神经发生的细胞程序。因此，Sox 8具有独特的能力，在颅外胚层的转录网络向耳朵的身份重塑。
Responsible for the sense of hearing and balance, the inner ear is critically important for communication with the environment. In humans, developmental malformations of the ear have lifelong consequences, while age-related hearing defects affect a large proportion of the population. However, many of the underlying genetic mechanisms remain unknown, and no regenerative strategies are available. Here, we characterize the transcriptional and regulatory landscape of ear progenitors, providing unprecedented detail on the molecular aspects of early ear development. We identify the transcription factor Sox8 as a key regulator that initiates the ear program including ear neurogenesis. Our findings not only elucidate how cell fate decisions are regulated in the embryo but can also inform reprogramming and regenerative strategies for the ear. The vertebrate inner ear arises from a pool of progenitors with the potential to contribute to all the sense organs and cranial ganglia in the head. Here, we explore the molecular mechanisms that control ear specification from these precursors. Using a multiomics approach combined with loss-of-function experiments, we identify a core transcriptional circuit that imparts ear identity, along with a genome-wide characterization of noncoding elements that integrate this information. This analysis places the transcription factor Sox8 at the top of the ear determination network. Introducing Sox8 into the cranial ectoderm not only converts non-ear cells into ear progenitors but also activates the cellular programs for ear morphogenesis and neurogenesis. Thus, Sox8 has the unique ability to remodel transcriptional networks in the cranial ectoderm toward ear identity.
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影响因子：
64.5
作者：
Benayoun BA;Pollina EA;Ucar D;Mahmoudi S;Karra K;Wong ED;Devarajan K;Daugherty AC;Kundaje AB;Mancini E;Hitz BC;Gupta R;Rando TA;Baker JC;Snyder MP;Cherry JM;Brunet A
通讯作者：
Brunet A
影响因子：
4.6
作者：
Delile, Julien;Rayon, Teresa;Sagner, Andreas
通讯作者：
Sagner, Andreas
DOI：
10.1007/5584_2019_374
发表时间：
2020-01-01
期刊：
CELL BIOLOGY AND TRANSLATIONAL MEDICINE, VOL 6: STEM CELLS: THEIR HETEROGENEITY, NICHE AND REGENERATIVE POTENTIAL
影响因子：
--
作者：
Bajohr, Justine;Faiz, Maryam
通讯作者：
Faiz, Maryam
DOI：
10.1002/dvdy.24306
发表时间：
2015-10
期刊：
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子：
--
作者：
Chen J;Streit A
通讯作者：
Streit A
影响因子：
6.7
作者：
Appler JM;Goodrich LV
通讯作者：
Goodrich LV