Conserved cell types with divergent features in human versus mouse cortex

By R. Hodge, Trygve E Bakken, Jeremy A. Miller, Kimberly A. Smith, Eliza R. Barkan, Lucas T. Graybuck, J. Close, Brian R. Long, Nelson J. Johansen, Osnat Penn and 54 more. Nature, 2019

1,546 citations recorded by the source corpus.

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. RNA-sequencing analysis of cells in the human cortex enabled identification of diverse cell types, revealing well-conserved architecture and homologous cell types as well as extensive differences when compared with datasets covering the analogous region of the mouse brain.

Subfields: Molecular Biology, Neurology

View Paper: https://www.semanticscholar.org/paper/5137a1182aabaab3bc3899d860652760a0b28134

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. Lars Bolund
2. Zizhen Yao
3. Cheng Zhang
4. Xun Xu
5. Hongkui Zeng
6. Xin Liu
7. Susan Sunkin
8. Adil Mardinoglu

Citations in the corpus

• An atlas of the protein-coding genes in the human, pig, and mouse brain (2020, background): “More recently, brain atlas strategies have been launched on the basis of different approaches: fluorescence-activated cell sorting in mouse (7), antibody-based cell sorting in human (8), single-cell gene expression in mouse (9) and human (10, 11), and covariation analysis of transcriptomics expressi”
• Cell segmentation in imaging-based spatial transcriptomics (2021, methodology): “Tissue processing was performed as previously described 38 , with some modifications.”
• A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation (2020, positive): “…(scRNA-seq) approach to systematically characterize and classify cell types in individual regions of the isocortex and hippocampus (Harris et al., 2018; Hodge et al., 2019; Tasic et al., 2016, 2018; Zeisel et al., 2015) (Yao et al, https://www.biorxiv.org/content/10.1101/2020.02.29.970558v2).”
• Transcriptome-scale spatial gene expression in the human dorsolateral prefrontal cortex (2020, methodology): “Heatmap of Pearson correlation values evaluating the relationship between our derived layer-enriched statistics (y-axis) for 700 genes and (B) layer-enriched statistics from snRNA-seq data in human medial temporal cortex produced by Hodge et al. (Hodge et al., 2019) (these data only profiled layers ”