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Conserved cell types with divergent features between human and mouse cortex

By Rebecca D Hodge, Trygve E. Bakken, Jeremy A. Miller, Kimberly A Smith, Eliza R Barkan, Lucas T. Graybuck, Jennie L. Close, Brian Long, Osnat Penn, Zizhen Yao, Jeroen Eggermont, Thomas Hollt, Boaz P. Levi, Soraya I Shehata, Brian Aevermann, Allison Beller, Darren Bertagnolli, Kristina Brouner, Tamara Casper, Charles Cobbs, Rachel Dalley, Nick Dee, Song-Lin Ding, Richard G Ellenbogen, Olivia C Fong, Emma Garren, Jeff Goldy, Ryder P Gwinn, Daniel Hirschstein, C. Dirk Keene, Mohamed Keshk, Andrew L. Ko, Kanan Lathia, Ahmed Mahfouz, Zoe Maltzer, Medea McGraw, Thuc Nghi Nguyen, Julie Nyhus, Jeffrey Ojemann, Aaron Oldre, Sheana Parry, Shannon Reynolds, Christine Rimorin, Nadiya V Shapovalova, Saroja Somasundaram, Aaron Szafer, Elliot R. Thomsen, Michael Tieu, Richard H. Scheuermann, Rafael Yuste, Susan Sunkin, Boudewijn Lelieveldt, David Feng, Lydia Ng, Amy Bernard, Michael Hawrylycz, John W. Phillips, Bosiljka Tasic, Hongkui Zeng, Allan R. Jones, Christof Koch, Ed S Lein

Posted 05 Aug 2018
bioRxiv DOI: 10.1101/384826 (published DOI: 10.1038/s41586-019-1506-7)

Elucidating the cellular architecture of the human neocortex is central to understanding our cognitive abilities and susceptibility to disease. Here we applied single nucleus RNA-sequencing to perform a comprehensive analysis of cell types in the middle temporal gyrus of human cerebral cortex. We identify a highly diverse set of excitatory and inhibitory neuronal types that are mostly sparse, with excitatory types being less layer-restricted than expected. Comparison to a similar mouse cortex single cell RNA-sequencing dataset revealed a surprisingly well-conserved cellular architecture that enables matching of homologous types and predictions of human cell type properties. Despite this general conservation, we also find extensive differences between homologous human and mouse cell types, including dramatic alterations in proportions, laminar distributions, gene expression, and morphology. These species-specific features emphasize the importance of directly studying human brain.

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