Single-cell epigenomics identifies a premetastatic regulatory program in lung adenocarcinoma [scATAC-seq]

Here we use an improved single-cell chromatin profiling approach to determine epigenomic alterations across tumor progression in a mouse model of lung adenocarcinoma (LUAD). Specifically, we induced tumors by providing Adeno-SPC-Cre virus to mice intratracheally to induce tumors due to conditional expression the Kras G12D mutation and loss of p53 (termed the KPT model). Mice also expressed a tdTomato reporter allele allowing for the sorting of tumor cells in late-stages of tumor progression. Using a combinatorial indexing approach (sciATAC-seq), we identify an epigenomic continuum representing a loss of cellular identity and progression towards a metastatic state. Biorad droplet based scATAC-seq on tumor-burdened lung from 8 week time point. Sorted tdTom positive tumor cells were profiled for chromatin accessibility changes.