A data-driven single-cell and spatial transcriptomic map of the human prefrontal cortex
Authors: Huuki-Myers Louise A. , Spangler Abby , Eagles Nicholas J. , Montgomery Kelsey D. , Kwon Sang Ho , Guo Boyi , Grant-Peters Melissa , Divecha Heena R. , Tippani Madhavi , Sriworarat Chaichontat , Nguyen Annie B. , Ravichandran Prashanthi , Tran Matthew N. , Seyedian Arta ,   PsychENCODE Consortium†, Hyde Thomas M. , Kleinman Joel E. , Battle Alexis , Page Stephanie C. , Ryten Mina , Hicks Stephanie C. , Martinowich Keri , Collado-Torres Leonardo , Maynard Kristen R. , Akbarian Schahram , Abyzov Alexej , Ahituv Nadav , Arasappan Dhivya , Almagro Armenteros Jose Juan , Beliveau Brian J. , Bendl Jaroslav , Berretta Sabina , Bharadwaj Rahul A. , Bhattacharya Arjun , Bicks Lucy , Brennand Kristen , Capauto Davide , Champagne Frances A. , Chatterjee Tanima , Chatzinakos Chris , Chen Yuhang , Chen H. Isaac , Cheng Yuyan , Cheng Lijun , Chess Andrew , Chien Jo-fan , Chu Zhiyuan , Clarke Declan , Clement Ashley , Collado-Torres Leonardo , Cooper Gregory M. , Crawford Gregory E. , Dai Rujia , Daskalakis Nikolaos P. , Davila-Velderrain Jose , Deep-Soboslay Amy , Deng Chengyu , DiPietro Christopher P. , Dracheva Stella , Drusinsky Shiron , Duan Ziheng , Duong Duc , Dursun Cagatay , Eagles Nicholas J. , Edelstein Jonathan , Emani Prashant S. , Fullard John F. , Galani Kiki , Galeev Timur , Gandal Michael J. , Gaynor Sophia , Gerstein Mark , Geschwind Daniel H. , Girdhar Kiran , Goes Fernando S. , Greenleaf William , Grundman Jennifer , Guo Hanmin , Guo Qiuyu , Gupta Chirag , Hadas Yoav , Hallmayer Joachim , Han Xikun , Haroutunian Vahram , Hawken Natalie , He Chuan , Henry Ella , Hicks Stephanie C. , Ho Marcus , Ho Li-Lun , Hoffman Gabriel E. , Huang Yiling , Huuki-Myers Louise A. , Hwang Ahyeon , Hyde Thomas M. , Iatrou Artemis , Inoue Fumitaka , Jajoo Aarti , Jensen Matthew , Jiang Lihua , Jin Peng , Jin Ting , Jops Connor , Jourdon Alexandre , Kawaguchi Riki , Kellis Manolis , Kleinman Joel E. , Kleopoulos Steven P. , Kozlenkov Alex , Kriegstein Arnold , Kundaje Anshul , Kundu Soumya , Lee Cheyu , Lee Donghoon , Li Junhao , Li Mingfeng , Lin Xiao , Liu Shuang , Liu Jason , Liu Jianyin , Liu Chunyu , Liu Shuang , Lou Shaoke , Loupe Jacob M. , Lu Dan , Ma Shaojie , Ma Liang , Margolis Michael , Mariani Jessica , Martinowich Keri , Maynard Kristen R. , Mazariegos Samantha , Meng Ran , Myers Richard M. , Micallef Courtney , Mikhailova Tatiana , Ming Guo-li , Mohammadi Shahin , Monte Emma , Montgomery Kelsey S. , Moore Jill E. , Moran Jennifer R. , Mukamel Eran A. , Nairn Angus C. , Nemeroff Charles B. , Ni Pengyu , Norton Scott , Nowakowski Tomasz , Omberg Larsson , Page Stephanie C. , Park Saejeong , Patowary Ashok , Pattni Reenal , Pertea Geo , Peters Mette A. , Phalke Nishigandha , Pinto Dalila , Pjanic Milos , Pochareddy Sirisha , Pollard Katherine S. , Pollen Alex , Pratt Henry , Przytycki Pawel F. , Purmann Carolin , Qin Zhaohui S. , Qu Ping-Ping , Quintero Diana , Raj Towfique , Rajagopalan Ananya S. , Reach Sarah , Reimonn Thomas , Ressler Kerry J. , Ross Deanna , Roussos Panos , Rozowsky Joel , Ruth Misir , Ruzicka W. Brad , Sanders Stephan J. , Schneider Juliane M. , Scuderi Soraya , Sebra Robert , Sestan Nenad , Seyfried Nicholas , Shao Zhiping , Shedd Nicole , Shieh Annie W. , Shin Joo Heon , Skarica Mario , Snijders Clara , Song Hongjun , State Matthew W. , Stein Jason , Steyert Marilyn , Subburaju Sivan , Sudhof Thomas , Snyder Michael , Tao Ran , Therrien Karen , Tsai Li-Huei , Urban Alexander E. , Vaccarino Flora M. , van Bakel Harm , Vo Daniel , Voloudakis Georgios , Wamsley Brie , Wang Tao , Wang Sidney H. , Wang Daifeng , Wang Yifan , Warrell Jonathan , Wei Yu , Weimer Annika K. , Weinberger Daniel R. , Wen Cindy , Weng Zhiping , Whalen Sean , White Kevin P. , Willsey A. Jeremy , Won Hyejung , Wong Wing , Wu Hao , Wu Feinan , Wuchty Stefan , Wylie Dennis , Xu Siwei , Yap Chloe X. , Zeng Biao , Zhang Pan , Zhang Chunling , Zhang Bin , Zhang Jing , Zhang Yanqiong , Zhou Xiao , Ziffra Ryan , Zeier Zane R. , Zintel Trisha M. 
Published: May 2024

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.