Single-cell epigenomics identifies a premetastatic regulatory program in lung adenocarcinoma [sciATAC-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. Overall design: sciATAC-Sequencing profiles of normal lung and lung adenocarcinoma murine samples. We profiled 44 individual samples including 2 normal murine lungs, 1 CD45 depleted murine lungs, and 44 tdTom sorted KPT lung primary lung and metastatic samples. Species mixing experiments were also completed with GM12878 and 3T3 cell lines.