Brain Cell Atlas: An Integrative Ensemble of Cell Transcriptomes Across Human Brain Regions

Abstract

Single-cell technologies greatly accelerated our understanding of the human brain cell types and their functions. But most studies focused on only a single or a couple of brain regions in a limited number of donors. Integration of atlas-level single-cell data can offer opportunities in revealing the cell type difference among brain regions, thus rendering explanations to the functional divergence. Here we present the Brain Cell Atlas (BCA), a comprehensive reference atlas of human brain cells, by assembling single-cell data from 70 studies of the human brain throughout major developmental stages across brain regions, covering over 11.3 million cells/nuclei from both healthy and disease. Using machine-learning based algorithms, BCA provides a consensus cell type annotation, while it showcases the discovery of a rare cell population of PCDH9high microglia cells. We demonstrate the gene regulatory difference of this cell type between hippocampus and prefrontal cortex as well as the cell-cell communications related to cell functions. In short, the BCA presents an atlas-level integrative resource for comparing brain cells in different environments and conditions within the Human Cell Atlas.