Spatially resolved mapping of cells associated with human complex traits

• 成果类型: Article
• 署名作者: Song, Liyang; Chen, Wenhao; Hou, Junren; Guo, Minmin; Yang, Jian
• 署名单位: Westlake University; Westlake Laboratory
• 刊物名称: Nature
• ISSN/ISSBN: 0028-1902
• DOI: 10.1038/s41586-025-08757-x
• 发表日期: 2025-05-22
• 关键词: ventral tegmental area; ca1 pyramidal neurons; EVOLUTION; transcriptomics; heritability; architecture; expression; DEPRESSION; stress; dorsal

摘要

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.