2019
DOI: 10.1038/s41586-019-1506-7
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Conserved cell types with divergent features in human versus mouse cortex

Abstract: Elucidating the cellular architecture of the human cerebral cortex 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 cortex. We identified 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 similar mouse cortex single cell RNA-sequ… Show more

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Cited by 1,440 publications
(2,067 citation statements)
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References 68 publications
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“…Interestingly and consistent with the observations in cross species scRNAseq analysis (Butler et al, 2018;Hodge et al, 2019), clustering without Seurat integration generated nearly non-overlapping mice and zebrafish clusters (Figure 4B and Figure S4), which is likely due to experimental differences between studies (e.g. cellular sequencing depth) as well as nonhomologous transcriptomes between species.…”
Section: Conservation Of Cell Types Across Speciessupporting
confidence: 86%
“…Interestingly and consistent with the observations in cross species scRNAseq analysis (Butler et al, 2018;Hodge et al, 2019), clustering without Seurat integration generated nearly non-overlapping mice and zebrafish clusters (Figure 4B and Figure S4), which is likely due to experimental differences between studies (e.g. cellular sequencing depth) as well as nonhomologous transcriptomes between species.…”
Section: Conservation Of Cell Types Across Speciessupporting
confidence: 86%
“…While we utilized RNAscope technology for fluorescent probe labeling, non-commercial smFISH technologies have also proven successful in postmortem human brain tissue 4 . However, RNAscope offers a rapid, robust, and universal approach that has now been replicated by several groups for qualitative validation of RNA-seq data in postmortem human brain tissue [3][4][5]18 .…”
Section: Dodotdot Overcomes Tissue Autofluorescence To Accurately Promentioning
confidence: 99%
“…In the age of rapidly advancing Next Generation Sequencing (NGS) technologies, such as single cell RNA-sequencing (RNA-seq) and spatial transcriptomics 1,2 , single-molecule fluorescent in situ hybridization (smFISH) has emerged as a potential gold standard for validating and extending findings derived from large scale transcriptomic data. The widespread generation of single-cell RNA-seq data sets in the neurosciences has fueled a resurgence of smFISH approaches to validate cell type-specific molecular profiles by visualizing individual transcripts at cellular resolution 3,4 . Information from single-cell RNA-seq data has revealed increasingly complex transcriptomic signatures for functionally distinct cell types, including the recently identified Rosehip neurons in cortical layer one 5 and cells with neurogenic potential in the dentate gyrus of the hippocampus 6,7 , such that molecular definition of these cells necessitates combinatorial labeling with multiple probes to confirm both presence and absence of specific transcripts within a spatially-defined context.…”
Section: Introductionmentioning
confidence: 99%
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“…However, rodents cannot reproduce the complexity of the human brain because brain development, anatomy and physiology differs greatly between animals and humans (Hodge et al, 2019). Hence, findings are not always transferable to the human condition and the success rate of preclinical trials is very low.…”
Section: Introductionmentioning
confidence: 99%