In their report BRAIN 2025: A Scientific Vision, the BRAIN Initiative working group of the Advisory Committee to the NIH Director outlined the first scientific goal as “Discovering Diversity: Identify and provide experimental access to the different brain cell types to determine their roles in health and disease.” Hence, the first scientific priority area (Cell Type) of the BRAIN Initiative was identified and the modalities of interest include: (1) molecular signatures (e.g., transcriptome, epigenome, proteome, metabolome), (2) anatomy (e.g., cell location, size, orientation, morphology, and connectivity), and (3) function.>
Recent technological advances in high throughput analyses of molecular, anatomic, and physiological measurements at the single cell level promise to open a new era calling for a unified brain cell census.
In 2014, the NIH BRAIN Initiative awarded 10 grants to pilot classification strategies and generate data/metadata for this comprehensive brain cell census. From these pilot projects, multiple brain regions from different organisms were studied using a variety of advanced technologies, and awardees collaborated on defining standards to describe experiments and data sets.
In 2017, NIH expanded support for the collection of cell census data and development of relevant tools by launching a coordinated set of awards under the auspices of a BRAIN Initiative Cell Census Network (BICCN). The overarching goal of the network is to generate comprehensive 3D common reference brain cell atlases that will integrate molecular, anatomical, and functional data for describing cell types in mouse, human, and non-human primate brains.
The BICCN is composed of a group of centers and collaboratories that work together to achieve the common goal:
- Comprehensive (U19) Centers that focus on building up a comprehensive mouse brain cell atlas.
- Specialized (U01) Collaboratories that contribute cell census data for endpoints in the mouse brain not otherwise covered in the U19 Centers.
- Specialized (U01) Collaboratories that begin to collect cell census data from human or non-human primate brains.
- A U24 BRAIN Cell Data Center (BCDC) that integrate, visualize, and disseminate the cell census data generated by the U19 and U01 Centers and Collaboratories as well as create a brain cell knowledge base.
The BICCN operates as a cooperative network to promote collaboration and coordination among the projects within the network and the BRAIN Initiative, as well as with any research entities that have similar goals.
BICCN Expected Outcomes
- Fundamental knowledge on diverse cell types and their three-dimensional organizational logic in the brain.
- An open-access 3D digital brain cell reference atlas with molecular, anatomical, and physiological annotations of brain cell types in mouse.
- A comprehensive neural circuit diagram in mouse brain.
- Reagents for cell-specific targeting.
- Validated high throughput and low-cost approaches to characterizing cell diversity in human and/or non-human primate brain samples.
Yong Yao, Ph.D.
National Institute of Mental Health (NIMH)