BICCN Data Inventory

Learn about and access data from the network of BICCN centers and laboratories. Data spans multiple species, modalities, and techniques.

Retrograde tracers injected into the mouse brain backfill the cell bodies of their input projections and fluoresce, as shown here. A combination of classical tracing techniques combined with novel rabies methods allows for the systematic elucidation of specific neuronal circuits, anatomy, and morphology. By injecting several different tracers into a single subject, the projections from the cortex can be shown with precise spatial relativity, further enriching the data that can be captured from each subject.

U19 - Ecker

Regulatory elements controlling gene expression can be detected by identification of regions of open chromatin (scATAC-seq), or changes in the level of cytosine methylation (scmC-seq) in the genomes of single cells. Applying these complimentary state-of-the-art DNA sequencing techniques to record the pattern in individual brain cell nuclei generates an epigenetic fingerprint for each cell. These fingerprints can be used to classify unique cell types and, when linked to specific neuronal circuits across brain regions, lead to the discovery of new genetic determinants of neuronal cell function.

U19 - Huang

Three cell-type specific axon projection patterns from motor cortex using multiplexed anterograde cre/flp-dependent viral tracers mapped to the common coordinate framework.

U01 - Feng

To help fill the evolutionary gap in knowledge between rodents and humans, high-throughput single-cell RNA sequencing will be used to identify cell types across 16 regions of the adult marmoset brain. Spatially mapping of these cell types in the brain will be performed using multiplexed fluorescent in situ hybridization. By combining viral expression we will also correlate cell morphology with this genetic information. Altogether these efforts will produce a census of cell types in the marmoset brain.

U01 - Kriegstein

Photo primary slice culture tissue stained to show fiber architecture (green), progenitor cells (red), and neurons (blue). Understanding human brain development is crucial to understanding stem cell function, how neurons and glia are made, and as a foundation for potential regeneration medicine therapies. The structure of a cortical brain slice, shown here, shows a sliver of the dynamic cell types, behaviors, and organization that emerges during brain development.

U01 - Lein

Triple modality Patch-seq experiment on a human layer 2 pyramidal neuron in temporal cortex (left). Triple modality Patch-seq experiment on a human layer 3 fast-spiking interneuron in temporal cortex (right). These examples demonstrate the successful recovery of detailed cellular morphology (a,d), electrophysiology (b,e), and single nucleus transcriptome (c,f) from human neocortical neurons. The single nucleus RNA-seq data from each Patch-seq experiment is used to map the experimental sample to a reference dendrogram of human middle temporal gyrus transcriptomic cell types.

U01 - Osten

Brain wide spatial distribution of neuronal cell types.

U19 - Zeng

Whole brain morphology reconstruction demonstrating multiple cell types in the isocortex. Two distinct cell types were identified based on their whole brain projection patterns. One type has projections restricted to ipsilateral cortex, while the other type sends projections to the homotypic region of the contralateral cortex.

U01 - Yang

An example of a genetically sparse-labeled D2-medium spiny neurons (MSN) imaged from a MORF (Mosaicism with Repeat Frameshift) mouse developed by the Yang lab.

U01 - Li Zhang

Schematic of the proposed study (left). Anterograde transsynaptic labelling of spinal cord neurons with AAV1-Cre (right).

U01 - Fischl

Example of transfer of information from micron-scale imaging to in vivo studies. Five cortical areas were manually labeled in the OCT AIP image (1), then registered to ex vivo MRI of the hemisphere that it was taken from (2). The areas were sampled onto an ex vivo surface model for that subject (3). Surface-based registration is then used to map these labels to models derived from in vivo ADNI subjects (4). This approach, when enabled by our proposed technology, will allow us and others to carry out morphometry studies in these predicted regions (5) revealing disease effects on laminar structure, cell density and myelin content.

U01 - Chung

Proteomic reconstruction of the human brain: integrated mapping of many cell-types in human visual cortex using the SWITCH technology (Murray, Cell, 2015)

U01 - Kun Zhang

Single-cell analyses to resolve cellular diversity in the adult human brain. Brain tissues are imaged and spatially registered using MRI, and sampling regions (visual cortex or BA17) are processed for single cell assays. Gene expression and chromatin accessible site mapping permits unbiased clustering of nuclei (visualized using t-SNE) and cell type annotation. Integration of these expression and regulation profiles provides more detailed molecular annotation of the cell types that can then be spatially mapped to the brain tissue sections using DART-FISH.

U01 – Ecker

Epigenomic profiling of human brain cells identifies cell-type specific gene regulatory regions. Analysis of the unique genetic profile of individual cell types supports the discovery of genetic variants associated with brain health and disease at the cellular level.

U01 - Snyder-Mackler

Single cell transcriptomic and epigenomic data will directly inform the distribution and function of key cell types across the lifespan of a close non-human primate relative—the rhesus macaque. These lifespan atlases will support the development of molecular interventions that empower the study, and potentially treatment, of myriad brain disorders.

RF1 – Chung

Overlay of multi-round immunostained images registered based on preserved YFP signals. YFP: green, NeuN: red; Neurofilament-H: white; Calretinin: dark blue; Calbindin: light blue; GFAP: dark purple; Parvalbumin: light blue; SMI-32: yellow.

RF1 – Nowakowski

Neurons in the adult mouse cortex expressing DNA barcodes developed in the Nowakowski lab. Cells will be sequenced and lineages reconstructed based on shared barcodes, which are inherited from their radial glia progenitors.

RF1 – Mueller

Manual annotation remains the bottleneck in morphological studies of projection neurons in mammalian brains (Winnubst et. al., 2019, Cell). Principled, open-source computer vision techniques will be developed to accelerate neuron segmentation in sub-micron resolution images, producing traces like those shown here.

RF1 – Regev

A composite imaging transcriptomic measurement of gene expression in mouse cortex. The expression levels of multiple genes are measured simultaneously in each color channel. When a small series of such image composites are acquired, the expression levels of a larger complement of genes in each cell may be inferred computationally.

RF1 – Tasic

Distinct neuronal types labeled in the mouse brain via an enhancer-driven Flp recombinase delivered by retroorbital injection of adeno-associated virus to a transgenic reporter mouse. The bright tdTomato fluorescent reporter molecule fills the virally transduced cells, revealing the full neuronal architecture.

R24 – Ghosh

DANDI is a Web platform for scientists to share, collaborate, and process data from cellular neurophysiology experiments. DANDI works with BICCN and other BRAIN Initiative awardees to curate data using community data standards such as NWB and BIDS, and to make data and software for cellular neurophysiology FAIR (Findable, Accessible, Interoperable, and Reusable). DANDI will store electrical and optical cellular neurophysiology recordings and associated MRI and/or optical imaging data.

What's New

12/13/23 Publication of the Whole Mouse Brain Atlas papers

10/12/23 Publication of Human and NHP Cell Atlas papers

07/12/23 Data dashboard for BICCN data is available

NIH's Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative - Cell Census Network (BICCN) aims to provide researchers and the public with a comprehensive reference of the diverse cell types in human, mouse, and non-human primate brain. A network of integrated centers and laboratories including U01, RF1, and U19 data generating centers, R24 data archives, and a U24 Brain Cell Data Center (BCDC) are working collaboratively to generate, map, and share these data with the community.

A comprehensive understanding of brain cell types is essential to understand how neural circuits generate perception and complex behaviors. Identifying and characterizing brain cell types, with the means to target each cell type, will elucidate the functional interactions that give rise to the emergent properties of the central nervous system. Toward this end, the overarching goals of the BICCN are to:

Create a high-resolution atlas of cell types in the mouse brain using large-scale single-cell transcriptomic and epigenetic analysis, as well as systematic characterization of neuronal morphology, connectivity, and electrophysiology in a wide range of brain areas.
Generate a census of the number and location of cells for each type and develop new genetic tools that target these select cell types.
Create an atlas of human brain cell types in the adult and in development. Profile cellular diversity in several structures relevant for neurodegeneration and neuropsychiatric disease including the hippocampus and dorsolateral prefrontal cortex, and characterize the anatomical and physiological properties of these neurons in human tissue.
Profile cell types in non-human primates, spanning the evolutionary gap between mouse and humans and for future work on the genetics and circuits of the primate brain.

Each BICCN project contributes publicly accessible data to a multimodal classification of cell types based on transcriptomic and epigenetic, morphology and connectivity, and physiological signatures of cells.

Data, Tools, and Knowledge for Cell Types

The data generating projects associated with the BICCN and their specific cell type profiling techniques are shown below. Filled cells indicate ongoing and planned data generation in mouse, non-human primate, and human. More details for each project are available on the portal team pages.

The role of the BCDC is to provide public access to and organization of the complex data, tools, and knowledge derived by the BICCN. The BICCN Portal serves as an entry point for BICCN activities and provides access to BICCN datasets stored at the R24 data archives. As our knowledge of the relationship of BICCN data modalities is uncovered, cell type summary knowledge will be presented to help enhance our understanding of the role of cell types in the brain.

All BICCN data meeting suitable quality control standards is immediately available to the public through several R24 data archives and accessible through this site. The BICCN data archives include:

Transcriptomic and epigenomic data is available through the Neuroscience Multi-Omic (NeMo) Archive, a data repository focused on the storage and dissemination of -omic data generated from the BRAIN Initiative and related brain research projects.
Image modality datasets are available through the Brain Image Library (BIL), a public resource enabling researchers to deposit, analyze, mine, share and interact with large brain image datasets.
Neurophysiology data are available at DANDI: Distributed Archives for Neurophysiology Data Integration.
Electron Microscopy and X-Ray Microtomography data are available at Brain Observatory and Storage Service (BossDB).

Data Access

R24 data archives house BICCN data for all projects. Access the data here.

Tools and Analysis

View computational and visualization tools for exploring BICCN data.