Chromatin accessibility landscapes define stromal cell identities across tissues

Chromatin accessibility landscapes are pivotal in regulating gene expression and maintaining cellular identity across diverse tissues. Using single-cell ATAC sequencing (scATAC-seq), we profiled chromatin accessibility across nine murine organs, encompassing 51,248 cells, to decipher the cis-regulatory mechanisms underlying tissue-specific and cell type-specific functions. Our analysis uncovered 28 major cell types with distinct chromatin accessibility signatures, revealing conserved and unique regulatory patterns. We identified transcription factor (TF) motifs associated with these regions, highlighting TF dynamics in cell differentiation and organ-specific functions. Additionally, we demonstrated that chromatin accessibility can trace stromal cells, including endothelial cells and fibroblasts, back to their tissue of origin, offering new insights into tissue-specific epigenomic landscapes. This innovative approach of leveraging epigenomic features to trace cells of origin represents a significant advancement, providing valuable insights into both normal and pathological states where identifying the tissue of origin is critically important.