Molecular studies of human tissues are necessary for understanding the details of human brain function in the context of specific pathways and cell types and how they are affected in disease conditions. Here we describe the creation of an anatomically comprehensive transcriptional map in a small number of carefully selected, clinically unremarkable specimens, applying standardized digital molecular brain atlasing methods used in model organisms3, 24, 25. The combination of histology-guided fine neuroanatomical molecular profiling and mapping of gene expression data into MRI coordinate space produced an anatomically accurate quantitative map of transcript distribution across the entire human brain. This strategy was borne out in the robust differential molecular profiles of cytoarchitecturally and functionally distinct nuclei, providing a high-resolution genome-wide map of transcript distribution and the ability to analyse genes underlying the function of specific brain regions. Similar application of RNA sequencing methods26, 27, which were cost-prohibitive and technologically immature when the project was initiated, holds great promise for elucidating finer details of transcriptional regulation in the future.
