Single-cell chromatin accessible state of paired primary and liver metastasis colorectal cancer cells from PDX cells derived mouse model

Chromatin regulatory networks that maintain differentiated cell states are frequently dysregulated in and thus contribute to cancer metastasis. Here, we reveal the dynamic transitions of regulatory states of colorectal cancer (CRC) cells during metastasizing to liver by profiling single-cell chromatin accessibility of paired primary and metastatic CRC tumors in mouse. We discover CRC subclones, which are characterized by losing chromatin accessibility around colon-tissue specific genes and gain that around liver-specific genes,including transcription factors in FOXA family and HNF family we discovered in our previous study, might partially mimic types of liver cells across the liver development. A particular subclone with stem-like state, which is highly enriched in metastases but not primary tumors , clearly shows poor prognosis. We used scATAC-seq to profile 3 paired primary and liver metastasis colorectal cancer cells of PDX cells derived mouse model.