Conserved cell types with divergent features in human versus mouse cortex

Rebecca D. Hodge, Trygve E. Bakken, Jeremy A. Miller, Kimberly A. Smith, Eliza R. Barkan, Lucas T. Graybuck, Jennie L. Close, Brian Long, Nelson Johansen, Osnat Penn, Zizhen Yao, Jeroen Eggermont, Thomas Höllt, Boaz P. Levi, Soraya I. Shehata, Brian Aevermann, Allison Beller, Darren Bertagnolli, Krissy Brouner, Tamara CasperCharles Cobbs, Rachel Dalley, Nick Dee, Song Lin Ding, Richard G. Ellenbogen, Olivia 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 G. Ojemann, Aaron Oldre, Sheana Parry, Shannon Reynolds, Christine Rimorin, Nadiya V. Shapovalova, Saroja Somasundaram, Aaron Szafer, Elliot R. Thomsen, Michael Tieu, Gerald Quon, Richard H. Scheuermann, Rafael Yuste, Susan M. 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

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)61-68
Number of pages8
JournalNature
Volume573
Issue number7772
DOIs
StatePublished - Sep 5 2019

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Hodge, R. D., Bakken, T. E., Miller, J. A., Smith, K. A., Barkan, E. R., Graybuck, L. T., Close, J. L., Long, B., Johansen, N., Penn, O., Yao, Z., Eggermont, J., Höllt, T., Levi, B. P., Shehata, S. I., Aevermann, B., Beller, A., Bertagnolli, D., Brouner, K., ... Lein, E. S. (2019). Conserved cell types with divergent features in human versus mouse cortex. Nature, 573(7772), 61-68. https://doi.org/10.1038/s41586-019-1506-7