A data-driven single-cell and spatial transcriptomic map of the human prefrontal cortex
Louise A. Huuki-Myers, Abby Spangler, Nicholas J. Eagles, Kelsey D. Montgomery, Sang Ho Kwon, Boyi Guo, Melissa Grant‐Peters, Heena R. Divecha, Madhavi Tippani, Chaichontat Sriworarat, Annie B. Nguyen, Prashanthi Ravichandran, Matthew N. Tran, Arta Seyedian, Thomas M. Hyde, Joel E. Kleinman, Alexis Battle, Stephanie C. Page, Mina Ryten, Stephanie C. Hicks, Keri Martinowich, Leonardo Collado‐Torres, Kristen R. Maynard, Schahram Akbarian, Alexej Abyzov, Nadav Ahituv, Dhivya Arasappan, José Juan Almagro Armenteros, Brian J. Beliveau, Jaroslav Bendl, Sabina Berretta, Rahul Bharadwaj, Arjun Bhattacharya, Lucy Bicks, Kristen Brennand, Davide Capauto, Frances A. Champagne, Tanima Chatterjee, Chris Chatzinakos, Yuhang Chen, H. Isaac Chen, Yuyan Cheng, Lijun Cheng, Andrew Chess, Jo-fan Chien, Zhiyuan Chu, Declan Clarke, Ashley Clement, Leonardo Collado‐Torres, Gregory M. Cooper, Gregory E. Crawford, Rujia Dai, Nikolaos P. Daskalakis, José Dávila-Velderrain, Amy Deep‐Soboslay, Chengyu Deng, Christopher P. DiPietro, Stella Dracheva, Shiron Drusinsky, Ziheng Duan, Duc M. Duong, Cagatay Dursun, Nicholas J. Eagles, Jonathan I. Edelstein, Prashant S. Emani, John F. Fullard, Kiki Galani, Timur R. Galeev, Michael J. Gandal, Sophia C. Gaynor, Mark Gerstein, Daniel H. Geschwind, Kiran Girdhar, Fernando S. Goes, William Greenleaf, Jennifer Grundman, Hanmin Guo, Qiuyu Guo, Chirag Gupta, Yoav Hadas, Joachim Hallmayer, Xikun Han, Vahram Haroutunian, Natalie Hawken, Chuan He, Ella Henry, Stephanie C. Hicks, Marcus Ho, Li‐Lun Ho, Gabriel E. Hoffman, Yi‐Ling Huang, Louise A. Huuki-Myers, Ahyeon Hwang, Thomas M. Hyde, Artemis Iatrou, Fumitaka Inoue, Aarti Jajoo, Matthew Jensen, Lihua Jiang, Peng Jin
Abstract
The 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.