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薄束核单细胞核转录组揭示兴奋性投射神经元多模块复合功能基因

司婷^1,2, 韩清见^1,2,*

¹复旦大学脑科学研究院-医学神经生物学国家重点实验室，上海 200032；²复旦大学脑科学前沿中心，上海 200032

摘要

薄束核(gracile nucleus, GR)作为体感通路中至关重要的第一级中继站，负责接收并处理来自下半身的精细触觉与本体感觉信号，其功能的精确性对于感知世界和协调运动至关重要。本研究利用单细胞核转录组测序(single-nucleus RNAsequencing, snRNA-seq)技术构建了成年小鼠GR的高分辨率转录组图谱。通过对细胞核的转录本进行深度测序和生物信息学分析，包括降维聚类、细胞类型注释、差异基因表达鉴定和功能分析，解构了GR的细胞构成。划分出主要的神经元和非神经元细胞类型，并在兴奋性投射神经元群体中鉴定出具有独特分子指纹和空间分布特征的亚型。功能基因富集分析进一步揭示了这些亚型在功能上的明确分工，一部分亚型构成了负责高速、高保真传递核心感觉信息的“传导型”主干通路，而另一部分亚型则富含多种神经肽(如生长抑素、胆囊收缩素等)，扮演着“调制型”角色。此外，研究发现这些神经元并非仅以离散亚型存在，而是沿着一个代表“感觉学习”或“感觉适应”过程的连续状态谱进行排列，其“适应”端显著富集了与突触可塑性和学习记忆相关的基因。本研究揭示了GR复杂细胞组织与内在可塑性，为深入理解躯体感觉系统的信息处理机制和慢性疼痛与感觉神经病变等相关疾病的病理生理学研究提供了新的见解和资源。

关键词： 薄束核; 单细胞核转录组; 兴奋性投射神经元; 功能基因集合; 多模块共表达; 本体感觉

Single-nucleus transcriptome of the gracile nucleus reveals multi-modular complex functional genes in excitatory projection neurons

SI Ting^1,2, HAN Qing-Jian^1,2,*

¹State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai 200032, China；²The MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China

Abstract

The gracile nucleus (GR), conventionally regarded as a primary relay in the ascending somatosensory pathway, plays a pivotal role in processing fine-touch, vibration, and proprioceptive information originating from the lower body. The fidelity of this processing is fundamental to sensory perception and motor coordination. We employed single-nucleus RNA sequencing (snRNA-seq) to establish a high-resolution, comprehensive transcriptomic atlas of the adult mouse GR. We systematically dissected the cellular architecture of the GR. Our analysis delineated all major neuronal and non-neuronal populations, and revealed a rich diversity of excitatory projection neuron subtypes, each characterized by a unique transcriptomic signature and a distinct spatial organization. Functional gene enrichment analysis unveiled a striking dichotomy in the roles of these subtypes. We identified a cohort of "conduction-type" neurons, specialized for the rapid and high-fidelity transmission of core somatosensory information, thereby preserving the integrity of the somatosensory map. In contrast, a second cohort of "modulatory-type" neurons demonstrated enriched expression of a diverse repertoire of neuropeptides, including somatostatin and cholecystokinin. These neurons are positioned to exert state-dependent modulation over the principal sensory pathways, fine-tuning information throughput in response to behavioral context or internal states such as arousal and attention. Notably, our findings reveal that these excitatory neurons do not exist as discrete, static populations. Instead, they are organized along a continuous transcriptional spectrum, which appears to represent a trajectory of sensory learning and adaptation. One pole of this continuum, representing an "adapted" state, exhibited significant enrichment of activity-dependent immediate-early genes integral to synaptic plasticity, learning, and memory, such as Fos, Arc, and Npas4. By elucidating this intricate cellular architecture and intrinsic plasticity, our study provides novel insights into information processing within the somatosensory system and offers a valuable resource for investigating the pathophysiology of related disorders, including chronic pain and sensory neuropathies.

Key words: gracile nucleus; single-nucleus transcriptome; excitatory projection neurons; functional gene sets; multi-module co-expression; somatosensation

收稿日期：　　录用日期：

通讯作者：韩清见　　E-mail:

DOI: 10.13294/j.aps.2026.0013

引用本文：

司婷, 韩清见. 薄束核单细胞核转录组揭示兴奋性投射神经元多模块复合功能基因[J]. 生理学报 2026; 78 (1): 207-220.

SI Ting, HAN Qing-Jian. Single-nucleus transcriptome of the gracile nucleus reveals multi-modular complex functional genes in excitatory projection neurons. Acta Physiol Sin 2026; 78 (1): 207-220 (in Chinese with English abstract).