The single-cell transcriptomic landscape of the topological differences in mammalian auditory receptors.

IF 8 2区 生物学 Q1 BIOLOGY Science China Life Sciences Pub Date : 2024-11-01 Epub Date: 2024-07-29 DOI:10.1007/s11427-024-2672-1
Xiangyu Ma, Xin Chen, Yuwei Che, Siyao Zhu, Xinlin Wang, Shan Gao, Jiheng Wu, Fanliang Kong, Cheng Cheng, Yunhao Wu, Jiamin Guo, Jieyu Qi, Renjie Chai
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Abstract

Mammalian hair cells (HCs) are arranged spirally along the cochlear axis and correspond to different frequency ranges. Serving as primary sound detectors, HCs spatially segregate component frequencies into a topographical map. HCs display significant diversity in anatomical and physiological characteristics, yet little is known about the organization of the cochleotopic map of HCs or the molecules involved in this process. Using single-cell RNA sequencing, we determined the distinct molecular profiles of inner hair cells and outer hair cells, and we identified numerous position-dependent genes that were expressed as gradients. Newly identified genes such as Ptn, Rxra, and Nfe2l2 were found to be associated with tonotopy. We employed the SCENIC algorithm to predict the transcription factors that potentially shape these tonotopic gradients. Furthermore, we confirmed that Nfe2l2, a tonotopy-related transcription factor, is critical in mice for sensing low-to-medium sound frequencies in vivo. the analysis of cell-cell communication revealed potential receptor-ligand networks linking inner hair cells to spiral ganglion neurons, including pathways such as BDNF-Ntrk and PTN-Scd4, which likely play essential roles in tonotopic maintenance. Overall, these findings suggest that molecular gradients serve as the organizing principle for maintaining the selection of sound frequencies by HCs.

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哺乳动物听觉受体拓扑差异的单细胞转录组图谱
哺乳动物的毛细胞(HCs)沿耳蜗轴呈螺旋状排列,对应不同的频率范围。作为主要的声音检测器,HC 在空间上将频率分隔成一个地形图。HCs在解剖和生理特征方面表现出显著的多样性,但人们对HCs耳蜗地形图的组织或参与这一过程的分子却知之甚少。通过单细胞 RNA 测序,我们确定了内毛细胞和外毛细胞不同的分子特征,并发现了许多以梯度方式表达的位置依赖性基因。新发现的基因(如 Ptn、Rxra 和 Nfe2l2)与音调相关。我们利用 SCENIC 算法预测了可能形成这些声调梯度的转录因子。此外,我们还证实了与音调相关的转录因子 Nfe2l2 对小鼠在体内感知中低频声音至关重要。对细胞-细胞通讯的分析揭示了连接内毛细胞和螺旋神经节神经元的潜在受体-配体网络,包括 BDNF-Ntrk 和 PTN-Scd4 等通路,这些通路可能在维持音调梯度方面发挥重要作用。总之,这些研究结果表明,分子梯度是维持内毛细胞选择声音频率的组织原则。
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来源期刊
CiteScore
15.10
自引率
8.80%
发文量
2907
审稿时长
3.2 months
期刊介绍: Science China Life Sciences is a scholarly journal co-sponsored by the Chinese Academy of Sciences and the National Natural Science Foundation of China, and it is published by Science China Press. The journal is dedicated to publishing high-quality, original research findings in both basic and applied life science research.
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