Single cell chromatin accessibility allows analysis of the transposable element landscape, revealing shared features of immune tissue residency

Tissue adaptation is a necessary process for immune cells to function within tissues and organs. Whether this process shares similarities between different tissue-localized immune cell populations is not yet well understood. Here, we addressed this by generating single cell ATAC-sequencing data of CD45+ tissue-localized immune cells from different tissues from mice and human donors. T cells, B cells, NK cells, and myeloid cells all showed bZIP transcription factor motif enrichment in tissue-localized cells. Tissue adaptation by regulatory T cells served as a reference program and comparisons unraveled shared features with other immune cell subsets, specifically with amphiregulin-producing Th17 and ILC2 cells. The ancient landscape of transposable elements (TE) revealed an enrichment of transcription factor binding motifs, especially bZIP family members, in accessible TE regions and identified individual TEs and TE families to be associated with tissue adaptation. Understanding tissue adaptation will help to harness immune cells in different disease contexts. Overall design: scATAC-seq of CD45+ hematopoietic cells from murine tissues such spleen, colon, visceral adipose tissue, and skin Treg naive 3 replicates, Tregs isolated from mice Foxp3tm1(CD2/CD52)Shori 3 replicates for tissue Treg and 1 (ATAC) 2 (ChIP) replicates for IL2 treated cells.