01969nas a2200409   4500000000100000008004100001260001500042100002600057700001800083700002300101700002500124700001700149700001300166700002500179700002100204700002000225700002700245700002000272700002800292700002000320700001800340700002700358700001900385700002100404700001800425700002200443700001500465700002300480700002100503700002800524700002300552245009200575856005600667300001300723490000800736520081500744       2024                            d  c2024-05-241 aLouise A. Huuki-Myers1 aAbby Spangler1 aNicholas J. Eagles1 aKelsey D. Montgomery1 aSang Ho Kwon1 aBoyi Guo1 aMelissa Grant-Peters1 aHeena R. Divecha1 aMadhavi Tippani1 aChaichontat Sriworarat1 aAnnie B. Nguyen1 aPrashanthi Ravichandran1 aMatthew N. Tran1 aArta Seyedian1 aPsychENCODE Consortium1 aThomas M. Hyde1 aJoel E. Kleinman1 aAlexis Battle1 aStephanie C. Page1 aMina Ryten1 aStephanie C. Hicks1 aKeri Martinowich1 aLeonardo Collado-Torres1 aKristen R. Maynard00aA data-driven single-cell and spatial transcriptomic map of the human prefrontal cortex  uhttps://www.science.org/doi/10.1126/science.adh1938  aeadh19380 v3843 aThe molecular organization of the human neocortex historically has been studied in the context of its histological layers. However, emerging spatial transcriptomic technologies have enabled unbiased identification of transcriptionally defined spatial domains that move beyond classic cytoarchitecture. We used the Visium spatial gene expression platform to generate a data-driven molecular neuroanatomical atlas across the anterior-posterior axis of the human dorsolateral prefrontal cortex. Integration with paired single-nucleus RNA-sequencing data revealed distinct cell type compositions and cell-cell interactions across spatial domains. Using PsychENCODE and publicly available data, we mapped the enrichment of cell types and genes associated with neuropsychiatric disorders to discrete spatial domains.