以单细胞分辨率绘制人类大脑皮层的空间转录组图谱。

Charting the spatial transcriptome of the human cerebral cortex at single-cell resolution.

作者信息

Wei Songren, Luo Meng, Wang Pingping, Chen Rui, Jin Xiyun, Xu Chang, Li Chenyang, Lin Xiaoyu, Xu Zhaochun, Liu Hongxin, Cheng Rui, Yang Wenyi, Cai Yideng, Xue Guangfu, Huang Peng, Liu Zhigang, Sun Haoxiu, Xu Jiangping, Jiang Qinghua

机构信息

School of Interdisciplinary Medicine and Engineering, Harbin Medical University, Harbin, 150076, China.

NMPA Key Laboratory for Research and Evaluation of Drug Metabolism& Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.

出版信息

Nat Commun. 2025 Aug 19;16(1):7702. doi: 10.1038/s41467-025-62793-9.

Abstract

A high-resolution spatial physiological atlas of cortical neurons serves as an essential reference for studying neurological diseases and is crucial for a comprehensive understanding of the cortical functions and physiological mechanisms. Although previous studies have elucidated the cellular basis of individual cortex, the molecular characteristics and precise spatial organization of neural cells within multiple human cortex remain incompletely understood. Subcellular-level spatial transcriptomic sequencing and snRNA-seq enabled mapping of 14 human cortical regions, creating a single-cell atlas with transcriptomic data from 1,121,772 nuclei and spatial profiles from 1,888,306 cells to characterize neural cell organization. The atlas reveals distinct expression patterns and spatial arrangements of neural cell types. Glutamatergic neurons show precise laminar patterns, with similar expression in adjacent cortex. SST neurons fall into two transcriptional categories, corresponding to superficial and deep layer distributions. The atlas, integrated with functional networks, highlights correlations between neural cell types and cortical functions, uncovering cell-cell interactions and ligand-receptor patterns with regional differences in neuron-glia communication. It also deciphers transcriptomic differences and cellular composition in layer 4 and the stable subplate (layer 6b) across regions. Our findings offer insights into the cellular foundations of complex and intelligent regions within the human cortex.

摘要

皮质神经元的高分辨率空间生理图谱是研究神经疾病的重要参考,对于全面理解皮质功能和生理机制至关重要。尽管先前的研究已经阐明了个体皮质的细胞基础,但多个人类皮质内神经细胞的分子特征和精确空间组织仍未完全了解。亚细胞水平的空间转录组测序和单细胞核RNA测序(snRNA-seq)实现了对14个人类皮质区域的图谱绘制,创建了一个单细胞图谱,包含来自1,121,772个细胞核的转录组数据和来自1,888,306个细胞的空间图谱,以表征神经细胞组织。该图谱揭示了神经细胞类型的不同表达模式和空间排列。谷氨酸能神经元呈现出精确的分层模式,在相邻皮质中表达相似。SST神经元分为两个转录类别,分别对应于浅层和深层分布。该图谱与功能网络相结合,突出了神经细胞类型与皮质功能之间的相关性,揭示了细胞间相互作用以及神经元与神经胶质细胞通讯中具有区域差异的配体-受体模式。它还破译了各区域第4层和稳定亚板(第6b层)的转录组差异和细胞组成。我们的研究结果为人类皮质内复杂且智能区域的细胞基础提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7368/12365125/7d3ee349799f/41467_2025_62793_Fig1_HTML.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索