Center for Multi-Scale Multi-Omic Human and non-human primate Brain Atlas - Project Summary A detailed understanding of the functional, anatomical and molecular architectures of brain cells and their brain-wide organization is essential for interrogating normal human brain function and disease states. Extensive efforts have been made toward mapping brain cells through various approaches, resulting in invaluable databases that are yielding new insights. However, we still lack comprehensive human brain atlases that capture multi-level properties of individual cells while adequately representing human demographic diversity and individual variability. The goal of this proposal is to create fully integrated three-dimensional (3D) human and non-human primate (NHP) brain cell atlases at subcellular resolution by simultaneously mapping brain-wide function, structure, and high-dimensional features (e.g., proteomic, transcriptomic, spatial, morphological, microenvironment and nanoscopic information) of cells acquired from the same whole brains with complete coverage of all brain regions. Our team will accomplish this by seamlessly integrating multimodal data from state-of-the-art functional (for NHP brains), structural, diffusion MRI, and multiscale 3D proteomic/transcriptomic imaging technologies. Using the scalable technology pipelines, we will perform proteomic and transcriptomic imaging of (1) human brains acquired from a large number of demographically representative donors and (2) functionally characterized non-human primate brains. The proposed work will create the most comprehensive 3D human and NHP brain atlases to date, with unprecedented resolution and completeness. The atlases will establish inter-species homologies essential for the translation of insights derived from animal models to humans, and aid in identifying the cellular and molecular underpinnings of human cognition and susceptibility to disease. Additionally, the unprecedented, multiscale multi-omic datasets acquired from a large number of demographically representative human donors will enable population level inter-individual variation study and allow baseline characterization of cellular and subcellular features, providing an immediately useful reference frame for the research community to study disease-specific changes in cell composition, spatial distribution, and subcellular architectures. Finally, our team will work closely with existing BICAN centers to maximize synergy and utilization of scarce brain materials and enable true multimodal data integration.
