Harold Hodgkinson Professor Yale University New Haven, Connecticut, United States
Introduction: Spatial omics enabled the construction of cell atlases that provide insights into cell function, interactions, physiology, and pathophysiology within the context of brain tissue structure. Additionally, the capability to analyze multiple layers of omic data helps in unraveling the mechanisms that driving brain development, differentiation, regional specialization, and changes during disease.
Materials and
Methods: Herein, we developed the first of its kind technologies for spatial tri-omic profiling of chromatin accessibility, mRNA expression, and ~200 proteins (spatial ATAC-RNA-Pro-seq), as well as spatial tri-omic profiling of histone modifications, mRNA expression, and ~200 proteins (spatial CUT&Tag-RNA-Pro-seq) on the same brain tissue section at near single cell resolution.
Results, Conclusions, and Discussions: We utilized these technologies to create spatial tri-omic atlases of the mouse brain at various developmental stages, from early embryonic to juvenile periods (embryonic days 11, 12, 14, 16, 18, and postnatal days 0, 2, 5, 10, 21), and compared these with developmental stages of human brains. We also analyzed the spatial molecular and cellular atlases within the neuroinflammatory microenvironment of a lysolecithin mouse model at peak and remission stages. This analysis uncovered new gene regulation mechanisms that modify cell state, dynamics, and function in disease conditions. We explored the spatiotemporal dynamics of mouse brains and identified significant correlations between the lysolecithin mouse model and specific brain cell types. We also clarified the mechanisms leading to abnormal cell states, which were difficult to detect using single-modality methods. The datasets we created serve as valuable resources for studying brain function and disease in both mice and humans.
