Cell Taxonomies

The Allen Institute for Brain Science builds data-driven classifications of cell types in the mammalian brain, along with tools for their exploration and publications for deeper scientific insight. The resources and publications below provide tools and knowledge to explore the organization of cellular and molecular complexity in this amazing biological system.

The Allen Institute provides a series of tools for navigating and exploring cell types in the mammalian brain in context. This includes tools for (1) exploring a cell type’s gene expression and anatomic context, (2) exploring a cell type’s morphology and electrophysiology, (3) mapping cell type names to user-provided data sets, and (4) summarizing features of brain cell types across studies. Such taxonomy navigation tools and their associated cell type taxonomies are listed below.

Exploring cell types in the mammalian brain

The Allen Brain Cell (ABC) Atlas provides a platform for visualizing multimodal single cell data across the mammalian brain and aims to empower researchers to explore and analyze multiple whole-brain datasets simultaneously. This tool currently includes cell types in the whole mouse brain and in human neocortex. Data downloads and notebooks with tutorials and examples are available on GitHub.

Explore the ABC Atlas | GitHub

Assigning cell types to your data in health and disease

MapMyCells allows scientists worldwide to assign cell types to their own transcriptomics and spatial data by comparing their data to mouse and human brain reference taxonomies derived by the Allen Institute for Brain Science and BICAN. This web-based tool currently includes cell types in the whole mouse brain and in human neocortex.

For mapping cells to cell types in human or mouse primary motor cortex, try Azimuth. To map cells to other Allen Institute (or user generated) cell type taxonomies, try scrattch.mapping.

Map your data with: MapMyCells | Azimuth | scrattch.mapping

Visualizing transcriptomic taxonomies of the human and mouse forebrain

The Transcriptomics Explorer is a tool for visualization and analysis of large-scale single-cell or single nucleus RNA-Seq data and associated cell type annotation. This tool likely wil not be updated, but key features will be transitioned into the ABC Atlas. Five taxonomies in human and mouse forebrain are available for exploration, including three listed here.
Human MTG (SEA-AD) | Mouse cortex and hippocampus | Human M1

The RNA-Seq Data Navigator application developed in 2018 to explore transcriptional data in mouse primary visual cortex (VISp) and anterior lateral motor cortex (ALM) is available here, and in human middle temporal gyrus (MTG) is available here.

Gene-level (exon and intron) read counts and metadata for all samples is available at http://celltypes.brain-map.org/rnaseq/.

Explore features of cell types in primary motor cortex

The Cell Type Knowledge Explorer aggregates and summarizes multi-modal information about human, marmoset, and mouse cell types in the primary motor cortex, demonstrating broad conservation of molecular cell type identities across these three species. Each cell type has a unique Cell Type Knowledge Card, which provides summary text and visualizations of available data. These data generated as part of the BICCN are described in detail in the BICCN flagship publication.

Visit the Cell Type Knowledge Explorer

Morpho-electric characterization of mammalian neurons

To integrate historical definitions of cell types based on morphology and electrophysiology with transcriptomics-based taxonomies, we carried out experiments to capture transcriptomic, electrophysiological, and morphological characteristics of single neurons using a modified Patch-seq recording technique. By applying this Patch-seq approach to human, mouse, and non-human primate, we can explore the shared and distinctive features across species.

Initial efforts included methodological details and background information, as well as access to multimodal data (and metadata) from 4,435 mouse and 318 human cortical neurons. Data from addition cells in cortical and in other brain regions are gradually updated.

Learn More and Download Patch-seq Data

Explore historical morpho-electric patch clamp data in human and mouse cortex

Cytosplore Viewer

Cytosplore Viewer is a downloadable application that allows exploration of single cell RNA-Seq and spatial transcriptomics data from the Allen Cell Types Database and from associated Allen Institute and BICCN publications. Mutliple viewers spanning a variety of projects have been built, and more continue to be developed. Cytosplore was developed by a team from the Leiden Computational Biology Center, the Division of Image Processing at the Leiden University Medical Center, and the Computer Graphics and Visualization Group at the TU Delft in collaboration with the Allen Institute.

Learn about taxonomies

The mammalian brain is composed of various cell populations that differ based on their molecular, morphological, electrophysiological, and functional characteristics. Classifying these cells into types is one of the essential approaches to defining the diversity of brain’s building blocks. We refer to such classifications as cell type “taxonomies,” and resources for understanding what taxonomies are and how to use them are included below.

Interactive tutorial: Building a cellular taxonomy of the mouse visual cortex

An interactive cellular taxonomy visualization representing diversity in the mouse primary visual cortex allows you to browse this landscape, based on gene expression at the single cell level, using data from over 1,600 cells. This visualization will guide you through some of the data and insights from this study and provides a good example explaining how a cell type taxonomy is built.

Explore | Publication

Cell type taxonomies webinar series (Jan-May 2024, Virtual)

The Cell Type Taxonomies A-Z: Webinar Series features presentations by Allen Institute scientists & staff for a full guide to brain cell types and taxonomies, and how and why to use these resources in your research. Register to attend here, or view them later at the Allen Institute YouTube channel. The six webinars include:

Cell Types 101 | January 10, 2024
What is a taxonomy? | January 31, 2024
The techniques behind the Cell Type Knowledge Explorer | February 28, 2024
Cross-species cell types | March 27, 2024
What is your cell type: MapMyCells | April 24, 2024
Introduction to ABC Atlas | May 22, 2024

Cell Type Knowledge Explorer video tutorial

This video tutorial describes how to use the Cell Type Knowledge Explorer along with a bit about the data that went into the underlying cross-species, multimodal taxonomies in primary motor cortex. Need additional support? Please contact us!

Watch the video tutorial | Visit the Cell Type Knowledge Explorer | Additional support

Taxonomy standards and nomenclature

Data and metadata standards are critical for tracking and annotating cell types within a study and for integrating studies across groups, species, and organ systems. This section includes a set of taxonomy, ontology, and nomenclature standards and tools for implementing them on Allen Institute, BICAN, or user data.

Cell taxonomy, ontology, and nomenclature standards (2024+)

The Allen Institute and BICAN collaborators plan to release multiple cell type taxonomies across multiple species, brain structures, and developmental stages over the next few years. In parallel, several tools and standards are being built to ensure consistency across projects for us and for the community at large. Work is ongoing to integrate these components.

The Cell Annotation Schema (CAS) is an evolving standard for storing data and metadata related to cell type taxonomies that is under joint development through BICAN and the Human Cell Atlas.
The CCN2 taxonomy editor tool can annotate one or more cell type taxonomies in the context of ontologies. It is intended to replace Microsoft Excel and Google Sheets for taxonomy annotation.
The Brain Knowledge Platform will store all information about cells needs for the ABC Atlas, MapMyCells, and other BICAN applications. Information about how whole mouse brain data is stored can be found on GitHub.
Scrattch-taxonomy encapsulates in a single .h5ad file the essential components of a taxonomy required for downstream analysis in scrattch.mapping and elsewhere.

Cell taxonomy and nomenclature standards (2020-2023)

Single cell RNA sequencing (scRNA-Seq) technology has led to an exciting expansion of datasets, tools and approaches for identifying and classifying cell types. We present the Common Cell Type Nomenclature (CCN), a working framework for creating brain cell type nomenclature, and include examples using published datasets. Feedback on the CCN is encouraged on the Allen Community Forum. An updated, detailed description of the CCN is available in a publication by Miller, et al. (2020), in eLife.

Overview | Publication | Code | Feedback

Mammalian brain cell type taxonomies

The Allen Institute and BRAIN Initiative collaborators have created a series of cell type classifications for multiple brain regions in human, mouse, and non-human primate. Most recently this has culminated in the presentation of whole brain atlases that will be refined and expanded. Cell type taxonomies linked to at least one navigation tool are listed below in the context of their scientific publication.

A high-resolution transcriptomic and spatial atlas of cell types in the WHOLE MOUSE BRAIN

Using advanced technologies that profile individual cells, we unveiled an atlas cataloging the location and type of every cell in the adult mouse brain. From >8 million cells in multiple data modalities, the team identified over 5,300 cell types – far more than known before – and pinpointed their locations within the brain’s intricate geography. This study is part of a set of 10 papers in Nature that will likely define the mouse whole brain for years to come.

Publication | Publication package (BICCN) | ABC Atlas | MapMyCells | Download the data

Transcriptomic diversity of cell types across the ADULT HUMAN BRAIN

This study used single-nucleus RNA sequencing to systematically survey cells across the entire adult human brain. We sampled more than three million nuclei from approximately 100 dissections across the forebrain, midbrain, and hindbrain in three postmortem donors. Our analysis identified 461 clusters and 3313 subclusters organized largely according to developmental origins and revealing high diversity in midbrain and hindbrain neurons. This work provides the most comprehensive census of cells in adult human brain to date.

Publication | Publication package (BICCN) | GitHub (data and code) | CELLxGENE | HCA BioNetwork | HuBMAP ASCT+B

Transcriptomic cytoarchitecture reveals principles of HUMAN NEOCORTEX organization

This study used single cell transcriptomics and performed cellular characterization of eight areas in human neocortex to better understand cortical areal specialization. This work identified 24 highly consistent cell subclasses across structures. However, proportions of excitatory neuron subclasses varied substantially, and some glia showed distinct layer organization across areas. Primary visual cortex showed characteristic organization with major changes both excitatory and inhibitory types, reflecting the importance of vision for humans.

Integrated multimodal cell atlas of ALZHEIMER’S DISEASE

This study used single cell and spatial genomics tools alongside quantitative neuropathology to understand the impact of Alzheimer's disease progression on cell types in middle temporal gyrus and dorsolateral prefrontal cortex. We mapped >1.2 million cells per region from 84 aged donors to 125 transcriptional types and showed which cell types changed in their abundance and gene expression with increasing disease pathology. This manuscript accompanies a freely available public resource to explore these data and to accelerate progress in AD research at SEA-AD.org.

A multimodal cell census and atlas of the mammalian PRIMARY MOTOR CORTEX

This paper summarizes the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN) and leads a series of 17 studies published in Nature. In total >3 million cells were profiled across modalities and species and >200TB of data and analysis tools are made freely available. Much of this work can be explored in the Cell Type Knowledge Explorer.

Publication | Publication package (BICCN) | Cell Type Knowledge Explorer | Transcriptomics Explorer (Human) | Cytosplore

A taxonomy of transcriptomic cell types across the ISOCORTEX AND HIPPOCAMPAL FORMATION

This manuscript used two complementary single-cell RNA-sequencing approaches, SMART-seq and 10x, to profile ∼1.2 million cells covering all regions in the adult mouse isocortex and hippocampal formation and derived a hierarchical cell type taxonomy comprising 379 transcriptomic types.

Publication | Cluster summaries (shinyapps.io) | Code | Transcriptomics Explorer | Download the data

Additional scientific publications

In addition to the mammalian brain taxonomies with associated resources described above, researchers at the Allen Institute share data via published peer-reviewed articles and pre-review open access services. Additional selected studies are included below.

Toward an integrated classification of neuronal cell types: morphoelectric and transcriptomic characterization of individual GABAergic cortical neurons

To better constrain the definition of neuronal cell types, we characterized the transcriptomes and intrinsic physiological properties of over 3,700 GABAergic mouse visual cortical neurons and reconstructed the local morphologies of 350 of those neurons. The data support the presence of at least 20 interneuron types that have congruent morphological, electrophysiological, and transcriptomic properties.

Publication | Allen SDK

Human cortical expansion involves diversification and specialization of supragranular intratelencephalic-projecting neurons

To probe the functional and anatomical correlates of the diverse set of transcriptomic cell types described in human cortex, a robust Patch-seq platform using neurosurgically-resected human tissues was built. This manuscript characterizes the morphological and physiological properties of five transcriptomically defined glutamatergic neuron types in layers 2 and 3 of human cortex and compares these properties with matched neuron types in mouse.

Publication | Allen SDK | Data Access | Code

Evolution of cellular diversity in primary motor cortex of human, marmoset monkey, and mouse

This manuscript uses high-throughput transcriptomic and epigenomic profiling of over 450,000 single nuclei in human, marmoset monkey, and mouse to demonstrate a broadly conserved cellular makeup of primary motor cortex (M1). It defines a cross-species consensus cell type classification, allowing inference of conserved cell type properties across species, and characterization of species specializations.

Publication | BICCN | Cytosplore

Classification of electrophysiological and morphological neuron types in the mouse visual cortex

To systematically profile morpho-electric properties of mammalian neurons, a single-cell characterization pipeline was built to generate data from patch-clamp recordings in brain slices, and biocytin-based neuronal reconstructions. This article presents the results of that study, with a taxonomy of morphologically and electrophysiologically defined cell types in the mouse cortex: 17 electrophysiological types, 38 morphological types and 46 morpho-electric types. Data from this publication can be explored in the Allen Cell Types Database.

Publication | Allen SDK

Cell type discovery using single-cell transcriptomics: implications for ontological representation

A review of recent studies of cellular diversity in the human brain and immune system using single cell and single nucleus RNA-sequencing. Discussion of a method to identify cell type specific marker genes and a proposal for naming and representing cell types in a structured Cell Ontology.

Publication | Provisional cell ontology

Shared and distinct transcriptomic cell types across neocortical areas

This work presents a high resolution cellular taxonomy of two regions of mouse cortex using single cell RNA-sequencing. Data in this work is included in the RNA-Seq Data Navigator tool for mouse, described above.

Publication | Code

Conserved cell types with divergent features between human and mouse cortex

This manuscript describes a cellular taxonomy of human cortex using single nucleus RNA-sequencing. Identification of matching cell types and cell classes between human and mouse is provided, and analysis of divergent expression between matching types. Data in this work is included in the RNA-Seq Data Navigator tool for human, described above.