Cooperative Agreements

PROJECT SUMMARY The developing mouse brain is a foundational experimental model for investigation of the origins of cell types in the mammalian brain. Comprehensive knowledge of mouse brain development is critical for comparative studies of neurodevelopmental processes, which are key to understanding the remarkable evolutionary innovations that distinguish humans from other species. In addition, developmental information enables refining cell taxonomy in the adult brain by incorporating knowledge of cell type and lineage origins into adult cell classification.

PROJECT SUMMARY/ABSTRACT The human brain exhibits profound diversity in biological function and vulnerability to disease. Despite the biomedical and cultural importance of inter-individual variation, we know relatively little about its underlying cellular and molecular substrates. In this work we will leverage new technologies in single-cell and spatial genomics to construct an Atlas of Human Brain Cell Variation. We will analyze tens of millions of cells from more than 200 people by single-nucleus RNA-seq and single-nucleus ATAC-seq, and a subset of these by spatial transcriptomics.

PROJECT SUMMARY This project will create scalable resources that will be critical to the development of BRAIN Initiative Cell Atlas Network (BICAN) consortium brain atlases. This team will focus on the development of common molecular data processing pipelines that are cloud-native and FAIR.

Progress in treating brain disorders has been frustratingly slow, in large part due to the extraordinary complexity of the human brain and its inaccessibility to study. Remarkable advances in technologies for studying individual cells, most notably single cell genomics, have revolutionized the study of complex nervous tissues and have been used to map cellular diversity across the entire mouse brain with cell types defined by their specific patterns of gene usage and gene regulatory mechanisms.

As a part of BRAIN 2.0, the BRAIN Initiative Cell Atlas Network (BICAN) is expected to advance fundamental knowledge and enabling technology for classifying human brain cell types, understanding their organizational principles, and providing open-access digital brain cell reference atlases, emphasizing c

Project Summary The ultimate product of our Center will be a series of comprehensive developing human and non-human primate (NHP) brain atlases of unprecedented cellular, spatial, and anatomical resolution. In Aim 1, we will characterize transient cell populations, establish the diversity of cell types present in specific brain regions, unravel complex developmental trajectories, and reveal conserved and divergent cell-type specific features. We will jointly profile of single nucleus RNA (snRNA-seq) and accessible chromatin (snATAC-seq) using the 10X Genomics snMultiome platform.

Abstract Understanding cell identities and their spatial distributions throughout different regions of the human brain is a fundamental step when trying to integrate physiological, behavioral, neurochemical and molecular data. At present, although major categories of the cell-types present in the human brain have been defined molecularly, the different subtypes within these categories along with their locations are far from understood. Gene expression drives cell programs and states that underlie distinct brain functions.

PROJECT SUMMARY The adult human brain is comprised of numerous cell types exhibiting specific transcriptomic and epigenomic signatures associated with their spatial location, connectivity, and function. Although systematic efforts are underway to characterize cell types in the adult human brain, the transitional cell types and cell states in developing human brains are not fully defined.

PROJECT SUMMARY The AAV BRAIN Safe and Effective Neuromodulator and Sensor Utilization across Species (SENSUS, led by Caltech) of the

Summary Demand for the common marmoset (Callithrix jacchus) in biomedical research has increased tremendously over the past five years, as they have emerged as a critical biomedical model system in a variety of study disciplines. The increased use of marmosets has been most acute in neuroscience, where the need to study cognition, behavior, and mental illness in primate models has grown.