bican

Introduction

BICAN is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

The Brain Initiative Cell Atlas Network (BICAN) is the successor to the BICCN, representing an expanded NIH BRAIN Initiative effort to create comprehensive cell type atlases of the mammalian brain across species, developmental stages, and disease states. Launched in 2023, BICAN builds upon the foundation established by BICCN while addressing critical gaps in coverage and integration^{1Brain Initiative Cell Atlas Network (BICAN). \"About BICAN.\"Open reference}.

While BICCN focused primarily on the adult mouse brain with limited human data, BICAN represents a major expansion in scope:

• Species coverage: Mouse, human, and multiple non-human primates (marmoset, macaque)

• Developmental range: From embryonic development through aging

• Disease focus: Emphasis on disease-affected tissue including Alzheimer’s and Parkinson’s disease brains

• Data integration: Enhanced frameworks for cross-species and cross-modality synthesis^{2BICAN (2023). "A consensus cell type atlas from multiple donors enabling cross-species integration." *Nature* 615: 73-812023 · Nature · DOI 10.1038/s41586-023-05973-5Open reference}

Historical Context

The BICAN emerged from lessons learned during the BICCN effort:

1. Human data gap: BICCN had limited human brain cell data — BICAN prioritizes human tissue

2. Species diversity: Non-human primates provide critical translational insights

3. Disease relevance: Direct study of disease-affected tissue rather than only healthy controls

4. Technical advances: New single-cell and spatial transcriptomics technologies enable larger-scale studies^{3"The BRAIN Initiative Cell Census Network: overflow requirements, tools and other topics - matters arising." *Nature* 615:e12022}

Consortium Structure and Institutions

Primary Institutions

BICAN brings together an expanded consortium:

• Allen Institute for Brain Science — Lead institution, data coordination

• University of California, San Diego — Human cell mapping

• University of Pennsylvania — Primate cell atlasing

• Harvard University — Single-cell genomics

• Stanford University — Spatial transcriptomics

• Broad Institute — Data integration and analysis

• University of Michigan — Developmental atlasing

• Janelia Research Campus — Advanced imaging

Research Areas

BICAN research priorities span:

• Human brain cell census — Comprehensive characterization of adult human cortical and subcortical cell types

• Non-human primate atlases — Marmoset and macaque cell type mapping

• Developmental trajectories — From neural stem cells to mature neurons

• Disease-focused atlasing — Direct study of AD, PD, and other neurodegenerative disease tissue^{4What is the BRAIN Initiative Cell Census Network (BICCN)?" *Cell* 185: 2658-26702022}

Major Goals and Achievements

1. Human Cell Type Census

A primary BICAN objective is comprehensive human brain cell mapping:

• 100+ brain regions — Expanded from BICCN’s limited cortical coverage

• Multiple cortical areas — Motor, sensory, association, limbic regions

• Subcortical structures — Thalamus, hypothalamus, basal ganglia

• Cellular diversity — Neuronal and glial cell type characterization

2. Cross-Species Integration

BICAN provides unprecedented cross-species comparison:

• Mouse-to-human translation — Validating findings in human tissue

• NHP models — Primate models for neurodegenerative disease

• Unified nomenclature — Standardized cell type names across species^{2BICAN (2023). "A consensus cell type atlas from multiple donors enabling cross-species integration." *Nature* 615: 73-812023 · Nature · DOI 10.1038/s41586-023-05973-5Open reference}

3. Disease Atlas Focus

Unlike its predecessor, BICAN directly incorporates disease tissue:

• Alzheimer’s disease — SEA-AD (Seattle Alzheimer’s Disease Brain Cell Atlas) as BICAN centerpiece

• Parkinson’s disease — Focus on dopaminergic neuron subtypes

• Other disorders — ALS, FTD, and related conditions

4. Developmental Coverage

BICAN extends beyond adult brains:

• Prenatal development — Human fetal brain cell mapping

• Postnatal maturation — Childhood and adolescent trajectories

• Aging — Comparison across the lifespan

Key Projects and Datasets

SEA-AD (Seattle Alzheimer’s Disease Brain Cell Atlas)

SEA-AD represents BICAN’s flagship disease atlas:

• 84+ donors — AD cases and cognitively normal controls

• 6 brain regions — Prefrontal cortex, temporal cortex, parietal cortex, hippocampus, entorhinal cortex, visual cortex

• ~100+ cell types — Comprehensive neuronal and glial characterization

• Multiple modalities — snRNA-seq, snATAC-seq, spatial transcriptomics^{5Converging insights from BRAIN Initiative Cell Census Network (BICCN) for cell types in the neocortex." *Neuron* 111: 5-92023}

SEA-AD provides unprecedented insights into:

• Cell type-specific changes in AD brains

• Vulnerable versus resilient cell populations

• Pathological protein distribution across cell types

• Genetic risk variant cell type specificity

Non-Human Primate Atlases

BICAN includes dedicated NHP projects:

• Marmoset brain atlas — New World monkey model

• Macaque brain atlas — Established translational model

• Cross-species comparison — Evolutionary relationships

Mouse Brain Atlas Enhancement

While BICAN emphasizes human data, mouse atlas work continues:

• Enhanced taxonomy — Refined cell type classification

• Cross-modal validation — Electrophysiology, morphology, transcriptomics

• Disease modeling — Transgenic and environmental models

Data Access and Resources

Primary Repositories

Resource	URL	Description
Brain Knowledge Platform	https://knowledge.brain-map.org/	BICAN unified data portal
CellxGene Census	https://cellxgene.cziscience.com/	CZI single-cell data portal
SEA-AD Portal	https://brain-map.org/consortia/sea-ad	AD-specific data
Allen Brain Atlas	https://portal.brain-map.org/	All Allen Institute data

Interactive Tools

• Atlas viewers for all species

• Gene expression browsers

• Cell type search engines

• Cross-species comparison tools

• Spatial transcriptomics visualization

Applications in Neurodegeneration Research

BICAN resources directly enable:

Understanding Disease Mechanisms

• Cell type specificity — Which cell types show pathology

• Selective vulnerability — Why specific neurons degenerate

• Genetic risk — Cell types expressing AD/PD risk genes

Therapeutic Development

• Target identification — Cell types requiring intervention

• Biomarker discovery — Cell type-specific markers in CSF/blood

• Model validation — Confirm mouse models reflect human disease

Precision Medicine

• Patient stratification — Cell type patterns predict progression

• Treatment response — Cell type involvement predicts drug response

• Personalized approaches — Individual patient cell atlases^{5Converging insights from BRAIN Initiative Cell Census Network (BICCN) for cell types in the neocortex." *Neuron* 111: 5-92023}

Comparison with BICCN

Feature	BICCN	BICAN
Primary species	Mouse	Human
Brain regions	~20	100+
Cell types	~300	500+
Disease focus	Limited	Extensive
Developmental	Adult only	Full lifespan
Non-human primates	Limited	Comprehensive

See Also

• Allen Institute](/institutions)

• BICCN — Predecessor project](/projects)

• SEA-AD — Flagship disease atlas](/projects)

• Allen Brain Atlas — Broader atlas initiative](/projects)

• Cell Types Database

External Links

• BICAN Official Website

• Brain Knowledge Platform](/technologies/brain-knowledge-platform)

• SEA-AD Portal

• Allen Institute BICAN

• BRAIN Initiative

Background

The BICAN represents a maturation of single-cell brain atlasing from proof-of-concept (BICCN) to comprehensive, disease-focused resource. By prioritizing human tissue and direct study of neurodegenerative disease, BICAN provides the most relevant data for understanding AD, PD, and related conditions.

Future directions include:

• Expansion to additional brain regions

• Integration of additional disease types

• Longitudinal sampling where possible

• Enhanced computational integration