A data-driven single-cell and spatial transcriptomic map of the human prefrontal cortex
Louise A. Huuki-Myers(Lieber Institute for Brain Development), Abby Spangler(Lieber Institute for Brain Development), Nicholas J. Eagles(Lieber Institute for Brain Development), Kelsey D. Montgomery(Lieber Institute for Brain Development), Sang Ho Kwon(Johns Hopkins University), Boyi Guo(Johns Hopkins University), Melissa Grant‐Peters(Great Ormond Street Hospital), Heena R. Divecha(Lieber Institute for Brain Development), Madhavi Tippani(Lieber Institute for Brain Development), Chaichontat Sriworarat(Johns Hopkins University), Annie B. Nguyen(Lieber Institute for Brain Development), Prashanthi Ravichandran(Johns Hopkins University), Matthew N. Tran(Lieber Institute for Brain Development), Arta Seyedian(Lieber Institute for Brain Development), Thomas M. Hyde(Johns Hopkins University), Joel E. Kleinman(Johns Hopkins University), Alexis Battle(Johns Hopkins University), Stephanie C. Page(Johns Hopkins University), Mina Ryten(Great Ormond Street Hospital), Stephanie C. Hicks(Johns Hopkins University), Keri Martinowich(Johns Hopkins University), Leonardo Collado‐Torres(Johns Hopkins University), Kristen R. Maynard(Johns Hopkins University), 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(Johns Hopkins University), 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(Johns Hopkins University), 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(Lieber Institute for Brain Development), 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(Johns Hopkins University), Qiuyu Guo(Johns Hopkins University), Chirag Gupta, Yoav Hadas, Joachim Hallmayer, Xikun Han(Johns Hopkins University), Vahram Haroutunian, Natalie Hawken, Chuan He(Lieber Institute for Brain Development), Ella Henry, Stephanie C. Hicks(Johns Hopkins University), Marcus Ho(Johns Hopkins University), Li‐Lun Ho(Johns Hopkins University), Gabriel E. Hoffman, Yi‐Ling Huang, Louise A. Huuki-Myers(Lieber Institute for Brain Development), Ahyeon Hwang, Thomas M. Hyde(Johns Hopkins University), Artemis Iatrou, Fumitaka Inoue, Aarti Jajoo, Matthew Jensen(Lieber Institute for Brain Development), Lihua Jiang, Peng Jin, Ting Jin, Connor Jops, Alexandre Jourdon, Riki Kawaguchi, Manolis Kellis, Joel E. Kleinman(Johns Hopkins University), Steven P. Kleopoulos, Alexey Kozlenkov(Johns Hopkins University), Arnold R. Kriegstein, Anshul Kundaje, Soumya Kundu, Che-Yu Lee, Donghoon Lee, Junhao Li(Great Ormond Street Hospital), Mingfeng Li(Great Ormond Street Hospital), Xiao Lin, Shuang Liu, Jason Liu, Jianyin Liu, Chunyu Liu, Shuang Liu, Shaoke Lou(Lieber Institute for Brain Development), Jacob M. Loupe, Dan Lu, Shaojie Ma(Johns Hopkins University), Liang Ma(Johns Hopkins University), Michael Margolis, Jessica Mariani, Keri Martinowich(Johns Hopkins University), Kristen R. Maynard(Johns Hopkins University), Samantha Mazariegos, Ran Meng(Lieber Institute for Brain Development), R Myers(Lieber Institute for Brain Development), Courtney Micallef, Tatiana Mikhailova, Guo‐li Ming, Shahin Mohammadi, Emma Monte, Kelsey S. Montgomery(Lieber Institute for Brain Development), Jill E. Moore, Jennifer Moran, Eran A. Mukamel, Angus C. Nairn, Charles B. Nemeroff, Pengyu Ni(Johns Hopkins University), Scott Norton, Tomasz J. Nowakowski, Larsson Omberg, Stephanie C. Page(Johns Hopkins University), Saejeong Park, Ashok Patowary, Reenal Pattni, Geo Pertea, Mette A. Peters(Great Ormond Street Hospital), Nishigandha Phalke, Dalila Pinto, Milos Pjanic, Sirisha Pochareddy, Katherine S. Pollard, Alex A. Pollen(Johns Hopkins University), Henry Pratt, Pawel F. Przytycki, Carolin Purmann, Zhaohui Qin, Pingping Qu, Diana Quintero, Towfique Raj, Ananya S. Rajagopalan, Sarah Reach, Thomas Reimonn(Johns Hopkins University), Kerry J. Ressler, D D Ross, Panos Roussos, Joel Rozowsky(Johns Hopkins University), Misir Ruth, W. Brad Ruzicka, Stephan Sanders, Juliane M. Schneider, Soraya Scuderi, Robert Sebra, Nenad Šestan, Nicholas T. Seyfried(Lieber Institute for Brain Development), Zhiping Shao, Nicole Shedd, Annie W. Shieh, Joo Heon Shin, Mario Škarica, Clara Snijders, Hongjun Song, Matthew W. State, Jason Stein, Marilyn Steyert, Sivan Subburaju, Thomas C. Südhof(Johns Hopkins University), M Snyder, Ran Tao(Lieber Institute for Brain Development), Karen Therrien, Li‐Huei Tsai, Alexander E. Urban, Flora M. Vaccarino, Harm van Bakel, Daniel Vo, Georgios Voloudakis, Brie Wamsley, Tao Wang, Sidney H. Wang, Daifeng Wang, Yifan Wang, Jonathan Warrell, Wei Yu, Annika K. Weimer, Daniel R. Weinberger, Cindy Wen, Zhiping Weng, Sean Whalen, Kevin P. White, A. Jeremy Willsey, Hyejung Won(Johns Hopkins University), Wing H. Wong, Hao Wu, Feinan Wu, Stefan Wuchty, Dennis Wylie, Siwei Xu, Chloe X. Yap, Biao Zeng, Pan Zhang(Lieber Institute for Brain Development), Chunling Zhang, Bin Zhang, Jing Zhang, Yanqiong Zhang, Xiao Zhou, Ryan Ziffra, Zane Zeier, Trisha M. Zintel
Cited by 64Open Access
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.