The single nuclei brain - Explore the expression profiles in single nuclei brain cell types

This resource contains brain cell type expression profiles based on single-nuclei RNA sequencing (snRNAseq) data covering 11 brain regions, including 2,5 million cells. The snRNAseq analysis, is based on genome-wide expression data published by Siletti K et al. (2023), representing the human brain with over 3 million cells and 461 clusters. In the Human Protein Atlas, the data is represented by 34 superclusters. A specificity classification was conducted to determine the number of genes with an elevated expression in these 34 main clusters across the brain regions, as displayed in the pie chart and table on this page. Gene expression and clustering within these different clusters can be further explored at the Human Brain Cell Atlas v1.0, where individual cell types, regions and clusters are provided. The integration of this extensive brain snRNAseq data facilitates easy comparison to the cell type expression profiles across different datasets. The Single cell type resource enables comparison to โ€œwhole bodyโ€ cell types, which includes integrated peripheral tissues and cerebral cortex snRNAseq data from Allen Brain Map. This Single nuclei brain data is expanding the brain cell details further, enabeling an in-depth comparison of clusters and regional variation across the human brain.

More information about the specific content, data generation, and analysis methods can be found in the Methods Summary, and in data details.

Explore the different knowledge summaries for cluster cell type by clicking the links in the table below, browse the list of genes with an elevated expression in different clusters by clicking the pie chart or bar chart below, or use the search function and find your favorite gene and see the regional expression overview for all the clusters. Additional links and background information can be found at the bottom of this page.

Learn about:

  • mRNA and protein expression in cell types within the human brain
  • if a gene is enriched in a particular cluster (specificity) compared to other cluster types in the brain
  • how the cluster specific expression varies across different brain regions
SINGLE NUCLEI BRAIN REGIONi


Classification of all protein-coding genes based on single cell type-specific expression, determining the number of genes elevated (cell type/group enriched, cell type enhanced) in a particular cell type compared to all other cell types.

0.02004006008001.0kgenesAmygdala excitatoryCerebellar inhibitoryCGE interneuronDeep-layer corticothalamic and 6bDeep-layer intratelencephalicDeep-layer near-projectingEccentric medium spiny neuronHippocampal CA1-3Hippocampal CA4Hippocampal dentate gyrusLAMP5-LHX6 and ChandelierLower rhombic lipMammillary bodyMedium spiny neuronMGE interneuronMidbrain-derived inhibitoryMiscellaneousSplatterThalamic excitatoryUpper rhombic lipUpper-layer intratelencephalicAstrocyteBergmann gliaCentral nervous system macrophageChoroid plexus epithelial cellCommitted oligodendrocyte precursorEpendymal cellOligodendrocyteOligodendrocyte precursor cellEndothelial cellPericyteVascular associated smooth muscle cellFibroblastLeukocyte

Cell type group
Cell type
Enriched
Group
enriched
Enhanced
Total
elevated
Neuronal cells Amygdala excitatory 073239
Cerebellar inhibitory 1830129177
CGE interneuron 102075105
Deep-layer corticothalamic and 6b 4196184
Deep-layer intratelencephalic 2104557
Deep-layer near-projecting 1016101127
Eccentric medium spiny neuron 12588114
Hippocampal CA1-3 2126680
Hippocampal CA4 320120143
Hippocampal dentate gyrus 718138163
LAMP5-LHX6 and Chandelier 125101127
Lower rhombic lip 937152198
Mammillary body 622118146
Medium spiny neuron 938147194
MGE interneuron 0216990
Midbrain-derived inhibitory 1133123167
Miscellaneous 043236
Splatter 9325697
Thalamic excitatory 103678124
Upper rhombic lip 1738194249
Upper-layer intratelencephalic 0107181
Glial cells Astrocyte 22187393602
Bergmann glia 18145363526
Central nervous system macrophage 1953165891100
Choroid plexus epithelial cell 99280405784
Committed oligodendrocyte precursor 6138158302
Ependymal cell 1882945471029
Oligodendrocyte 44122450616
Oligodendrocyte precursor cell 10100219329
Endothelial cells Endothelial cell 152249569970
Muscle cells Pericyte 25208328561
Vascular associated smooth muscle cell 39224337600
Mesenchymal cells Fibroblast 64234367665
Blood & immune cells Leukocyte 2673044681039

The brain includes different cell types, and subclasses of the different cells. Neurons are the main signaling units, communicating via synapses. The two main subclasses of neurons are interneurons (local interconnections between neurons) and projection neurons. Interneurons are often inhibitory neurons, meaning they work against the increase of membrane potential and likelihood of an action potential propagation in the postsynaptic neuron. While, projecting neurons often are excitatory neurons, raising the membrane potential in the postsynaptic neuron. Different brain regions contain different types of neurons, specialized for regional specific functions and circuitry. There are variations across the brain regions when it comes to the overlap of inhibitory and excitatory neuronal subtypes, and neurons are often classified based on their neurotransmitter used for signaling.

The non-neuronal cells in the brain are the endothelial cells lining blood vessels, pericytes and vascular associated smooth muscle cells that are closely related vasculature cells involved in contraction and circulation of the blood, fibroblasts surrounding the larger blood vessels and found in the choroid plexus structures, immune cells, both circulating and infiltrating the brain parenchyma, numerous glial cells; astrocytes, microglia, OPC, committed OPC, oligodendrocytes, Bergmann glia as well as ependymal cells lining the ventricular walls and choroid plexus epithelial cells. The main glial cell types are oligodendrocytes (insulating neuronal axons for faster signal transmission), microglia (the brain macrophage with a hematopoietic origin) and astrocytes which are involved in numerous functions such as blood brain barrier, homeostasis, neuronal growth and neurotransmitter recycling.


The figure illustrates the main cell types of the brain: ependymal cells in purple, endothelial cells in red, A=astrocytes in blue, M=microglia in brown, N=neuron in green and O=oligodendrocytes in orange.

Clusters across 11 different brain regions

Out of the 2.5 million cells included in the brain nuclei representation, 1733487 cells are neuronal, 769594 are glial cells and 20644 other cell types (vascular and immune cells). Although glial cells are numerous, the number of subclusters are fewer than for neuronal cells. Neurons across the different regions are divided into 21 different superclusters. In the UMAP to the left the cells are colored based on the grouped cell type, while the UMAP to the right show the individual cluster names below.




These UMAPs are based on the selected cells used for brain nuclei visualization in the Single cell resource of the Human Protein Atlas. All cells can be explored in the original paper and database: The Human Brain Cell Atlas v1.0 . The cluster names are not the same as cell types. Some clusters are translatable into a cell types, while others, especially the neuronal clusters, are more complex than that. However, the supercluster names are a good tool for a general expression overview across regions. Read more about the method behind the import of this data under Methods Summary.

Cell clusters in different brain regions

Expression profiles across cell clusters and brain regions are available for all protein-coding genes, searchable and clickable for more details. A bar chart of the cell clusters combined with regional details is shown in a bubble plot on each gene summary page, along with other single cell datasets.

The regional separation of the supercluster expression profiles enables exploration at a regional specific level of neuronal variation. As an example, the expression overview of somatostatin (SST) shows highest expression in the cluster called splatter and MGE interneurons, while at a regional level the SST expressing midbrain neurons mainly belonging to the MGE interneuron cluster.

0100200300400500600700nTPM
SST - SnBrain
02004006008001,0001,2001,400nTPM
SST - Midbrain


SST - midbrain

SST - hippocampus

Background

Single nuclei RNAseq data

Siletti K et al. (2023) published single nuclei RNA sequencing result, based on over 3 million cells from multiple brain regions, in Science magazine and created an interactive portal (The Human Brain Cell Atlas v1.0 ) available for single cell exploration across human gene expression in healthy brain cells. The Human Protein Atlas aims to generate a comprehensive resource representing the human body and its complexity, and with a need for better representation of the different cell types of the human brain, we imported the expression profiles and grouped them based on our cell type- strategy (providing bar charts of pooled data for each cell type cluster and calculating the average normalized protein-coding transcripts per million). We based the cell type clusters on the 31 superclusters, as well as the provided assigned cell types, and the data is shown as 34 different "supercluster cell types". The expression profile of the different clusters is shown for each of the 11 different brain regions. More details, related to number of M reads and number of cells per brain region/UMAP can be found here. The published cerebral cortex data is represented by a larger number of cells, and we only included a random selection of 500 thousand cells. In total, expression data for 2526725 brain cells is displayed in the Brain single nuclei resource, for browsing the gene expression and provide easy comparison to cell type expression in peripheral tissues.