Single-cell ATAC plus gene expression reveals differential epigenetic profiles of macrophages across tissue types 4001

Abstract Description Single-Cell Multiome combines single-cell gene expression with single-cell ATAC-seq to provide sequencing of both transcriptomal and epigenetic landscapes. Chromatin is mapped using ATAC-Seq, in which Tn5 transposase inserts adapters into open regions in situ. ATAC is performed on nuclei which are met with barcoded gel beads so that one nucleus enters one bead in which cDNA and ATAC libraries are constructed. Our lab has profiled over 16 different cell or tissue types, including PBMC, heart, liver, and brain and across 5 species (human, mouse, pig, snake, hamster). These combined datasets have been integrated revealing that immune cells occupy niches in tissues other than blood and bone marrow, these cells function differently across tissue types, and there are common features of these cells across tissue types and species. Our body of work is perhaps the most comprehensive atlas of combined single-cell epigenetic and gene expression data constructed. We focus here on one aspect of this cross-tissue and cross-species comparison. Monocytes arise from bone marrow and circulate in blood and give rise to macrophages and dendritic cells. When they migrate to the brain they become microglia. In the heart they become cardiac macrophages. We use our Multiome data sets to compare gene expression and epigenetic profiles of this cell type in human PBMC, mouse brain, and mouse heart. One gene, CSF1R, is an example of a defining feature of monocytes, microglia, and cardiac macrophages. Topic Categories Computational and Systems Immunology (COMP)