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 “whole body” 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.

Cell type group	Cell type	Enriched	Group enriched	Enhanced	Total elevated
Neuronal cells	Amygdala excitatory	0	7	32	39
	Cerebellar inhibitory	18	30	129	177
	CGE interneuron	10	20	75	105
	Deep-layer corticothalamic and 6b	4	19	61	84
	Deep-layer intratelencephalic	2	10	45	57
	Deep-layer near-projecting	10	16	101	127
	Eccentric medium spiny neuron	1	25	88	114
	Hippocampal CA1-3	2	12	66	80
	Hippocampal CA4	3	20	120	143
	Hippocampal dentate gyrus	7	18	138	163
	LAMP5-LHX6 and Chandelier	1	25	101	127
	Lower rhombic lip	9	37	152	198
	Mammillary body	6	22	118	146
	Medium spiny neuron	9	38	147	194
	MGE interneuron	0	21	69	90
	Midbrain-derived inhibitory	11	33	123	167
	Miscellaneous	0	4	32	36
	Splatter	9	32	56	97
	Thalamic excitatory	10	36	78	124
	Upper rhombic lip	17	38	194	249
	Upper-layer intratelencephalic	0	10	71	81
Glial cells	Astrocyte	22	187	393	602
	Bergmann glia	18	145	363	526
	Central nervous system macrophage	195	316	589	1100
	Choroid plexus epithelial cell	99	280	405	784
	Committed oligodendrocyte precursor	6	138	158	302
	Ependymal cell	188	294	547	1029
	Oligodendrocyte	44	122	450	616
	Oligodendrocyte precursor cell	10	100	219	329
Endothelial cells	Endothelial cell	152	249	569	970
Muscle cells	Pericyte	25	208	328	561
	Vascular associated smooth muscle cell	39	224	337	600
Mesenchymal cells	Fibroblast	64	234	367	665
Blood & immune cells	Leukocyte	267	304	468	1039

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.

SST - SnBrain
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.