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Nature. 2019 Sep;573(7772):61-68. doi: 10.1038/s41586-019-1506-7. Epub 2019 Aug 21.

Conserved cell types with divergent features in human versus mouse cortex.

Author information

1
Allen Institute for Brain Science, Seattle, WA, USA.
2
Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA, USA.
3
Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
4
Department of Intelligent Systems, Delft University of Technology, Delft, The Netherlands.
5
J. Craig Venter Institute, La Jolla, CA, USA.
6
Department of Pathology, University of Washington, Seattle, WA, USA.
7
The Ben and Catherine Ivy Center for Advanced Brain Tumor Treatment, Swedish Neuroscience Institute, Seattle, WA, USA.
8
Department of Neurological Surgery, University of Washington School of Medicine, Seattle, WA, USA.
9
Epilepsy Surgery and Functional Neurosurgery, Swedish Neuroscience Institute, Seattle, WA, USA.
10
Regional Epilepsy Center at Harborview Medical Center, Seattle, WA, USA.
11
Department of Pathology, University of California, San Diego, San Diego, CA, USA.
12
Neurotechnology Center, Department of Biological Sciences, Columbia University, New York, NY, USA.
13
Allen Institute for Brain Science, Seattle, WA, USA. edl@alleninstitute.org.

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.

PMID:
31435019
DOI:
10.1038/s41586-019-1506-7

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