韦斯特莱克大学研究团队报道了与人类复杂特征相关的细胞的空间分辨映射。相关论文于2025年3月19日发表在《自然》杂志上。

在这里，研究团队提出了复杂性状细胞的遗传信息空间定位（gsMap），这是一种将空间转录组学数据与全基因组关联研究的汇总统计数据相结合的方法，以空间解决的方式将细胞定位为人类复杂性状，包括疾病。利用涵盖25个器官的胚胎空间转录组学数据集，小组通过模拟和证实各种器官中已知的性状相关细胞或区域来对gsMap进行基准测试。将gsMap应用于大脑空间转录组学数据，该课题组发现与精神分裂症相关的谷氨酸能神经元的空间分布更接近于认知特征，而不是抑郁等情绪特征。精神分裂症相关的谷氨酸能神经元分布在海马背侧附近，钙信号和调控基因表达上调，而抑郁症相关的谷氨酸能神经元分布在前额叶内侧皮层深部，神经可塑性和精神药物靶基因表达上调。他们的研究为性状相关细胞的空间分辨图谱提供了一种方法，并展示了通过这些图谱获得的生物学见解（如性状相关细胞和相关特征基因的空间分布）。

据了解，描绘疾病相关细胞的空间分布对于理解疾病病理至关重要。

附：英文原文

Title: Spatially resolved mapping of cells associated with human complex traits

Author: Song, Liyang, Chen, Wenhao, Hou, Junren, Guo, Minmin, Yang, Jian

Issue&Volume: 2025-03-19

Abstract: Depicting spatial distributions of disease-relevant cells is crucial for understanding disease pathology1,2. Here we present genetically informed spatial mapping of cells for complex traits (gsMap), a method that integrates spatial transcriptomics data with summary statistics from genome-wide association studies to map cells to human complex traits, including diseases, in a spatially resolved manner. Using embryonic spatial transcriptomics datasets covering 25 organs, we benchmarked gsMap through simulation and by corroborating known trait-associated cells or regions in various organs. Applying gsMap to brain spatial transcriptomics data, we reveal that the spatial distribution of glutamatergic neurons associated with schizophrenia more closely resembles that for cognitive traits than that for mood traits such as depression. The schizophrenia-associated glutamatergic neurons were distributed near the dorsal hippocampus, with upregulated expression of calcium signalling and regulation genes, whereas depression-associated glutamatergic neurons were distributed near the deep medial prefrontal cortex, with upregulated expression of neuroplasticity and psychiatric drug target genes. Our study provides a method for spatially resolved mapping of trait-associated cells and demonstrates the gain of biological insights (such as the spatial distribution of trait-relevant cells and related signature genes) through these maps.

DOI: 10.1038/s41586-025-08757-x

Source: https://www.nature.com/articles/s41586-025-08757-x