Specification of neuronal subtypes in the spiral ganglion begins prior to birth in the mouse.
Specification of neuronal subtypes in the spiral ganglion begins prior to birth in the mouse.
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DOI：
10.1073/pnas.2203935119
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发表时间：
2022-11-29
影响因子：
11.1
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中科院分区：
文献类型：
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螺旋神经节神经元（SGN）负责将复杂的声音信息从耳蜗传递到听觉脑干，它们的损失导致年龄相关的和获得性听力损失。生理学、解剖学和分子生物学方法已经在成人耳蜗中鉴定出四种不同的SGN亚型。然而，这些亚型何时以及如何在发育过程中被指定是未知的。使用单细胞RNA-Seq，我们表征了SGN亚型规范的时间和顺序。我们进一步鉴定了可能调节下游基因的转录因子，这些转录因子在SGN分裂成特定亚型时由SGN差异表达。这项工作为SGN发育过程中的基因表达提供了全面的数据集和分析，这将是发育，再生和神经元功能研究的杰出资源。耳蜗的传入神经支配由螺旋神经节神经元（SGN）组成，其特征为四种亚型（1A型、B型和C型以及2型）。然而，很少有人知道的因素和/或过程，决定每个亚型。在这里，我们提出了一个转录分析约5,500个单一的小鼠SGN收集在四个发展的时间点。所有四种亚型在协调的自发活动开始之前都是转录可识别的，这表明初始的规范过程受到遗传控制。轨迹分析表明SGN最初分裂成两种前体类型（1A/2型和1B/C型），随后分裂产生四种转录上不同的亚型。差异基因表达，假时间，和调节子分析被用来确定候选转录因子，可能会调节亚型的规范过程。这些结果提供了深入了解SGN的发展，并包括整个产前期间SGN成熟的转录图谱。
Spiral Ganglion neurons (SGNs) are responsible for relaying complex sound information from the cochlea to the auditory brainstem, and their loss contributes to age-related and acquired hearing loss. Physiological, anatomical, and molecular approaches have identified four different subtypes of SGNs in the adult cochlea. However, when and how these subtypes become specified developmentally is unknown. Using single-cell RNA-Seq, we characterized the timing and order of SGN subtype specification. We further identified transcription factors that potentially regulate downstream genes and are differentially expressed by SGNs as they split into specific subtypes. This work contributes a comprehensive data set and analysis of gene expression across SGN development that will be an outstanding resource for studies of development, regeneration, and neuronal function. The afferent innervation of the cochlea is comprised of spiral ganglion neurons (SGNs), which are characterized into four subtypes (Type 1A, B, and C and Type 2). However, little is known about the factors and/or processes that determine each subtype. Here, we present a transcriptional analysis of approximately 5,500 single murine SGNs collected across four developmental time points. All four subtypes are transcriptionally identifiable prior to the onset of coordinated spontaneous activity, indicating that the initial specification process is under genetic control. Trajectory analysis indicates that SGNs initially split into two precursor types (Type 1A/2 and Type 1B/C), followed by subsequent splits to give rise to four transcriptionally distinct subtypes. Differential gene expression, pseudotime, and regulon analyses were used to identify candidate transcription factors which may regulate the subtypes specification process. These results provide insights into SGN development and comprise a transcriptional atlas of SGN maturation across the prenatal period.
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影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
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Brady, Gareth;Whiteman, Hannah J.;Farrell, Paul J.
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Farrell, Paul J.
影响因子：
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作者：
Milili, M;Gauthier, L;Schiff, C
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Schiff, C
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16.6
作者：
Defourny, Jean;Poirrier, Anne-Lise;Malgrange, Brigitte
通讯作者：
Malgrange, Brigitte
影响因子：
5.3
作者：
Druckenbrod, Noah R.;Goodrich, Lisa V.
通讯作者：
Goodrich, Lisa V.