Single-nucleus multiple-organ chromatin accessibility landscape in the adult rat.

BACKGROUNDChromatin accessibility landscape is the basis of cell-specific gene expression and reflects the regulatory logic underlying cellular identity and function. However, a systematic multi-organ chromatin accessibility atlas in the rat (Rattus norvegicus), an important biomedical model organism, has been lacking.

RESULTSWe generated a multi-organ single-nucleus chromatin accessibility landscape of Rattus norvegicus using snATAC-seq. For this single-cell atlas, we constructed 25 libraries via snATAC-seq from 9 organs in the adult rat, with a total of over 110,000 cells. Cell classification integrating gene activity scores with known marker genes identified 77 cell types, which were strongly correlated with those in published mouse single-cell transcriptome atlases. We further investigated the enrichment of cell-type- and organ-specific transcription factors, shared and organ-specific features of endothelial and stromal cells, as well as cross-organ macrophage regulatory states, and the conservation and specificity of gene regulatory programs across species.

CONCLUSIONThis single-nucleus chromatin accessibility landscape provides a valuable foundation for dissecting tissue-specific regulatory mechanisms in the rat and facilitates cross-organ and cross-species cell type annotation and functional inference, supporting broader applications of rat model in systems biology and biomedical research.