Single-nucleus RNA-seq analysis resolves chromatin and transcriptional features of fibrolamellar carcinoma

Fibrolamellar carcinoma (FLC) is a rare malignancy disproportionately affecting adolescents and young adults with no standard of care. FLC is characterized by thick stroma, which has long suggested an important role of the tumor microenvironment. Over the past decade, several studies have revealed aberrant molecular markers and pathways in FLC. However, an important limitation of these efforts is that they were conducted on bulk tumor samples. Consequently, the cell types that contribute to the different molecular features of FLC have remained unknown. In this study we primarily leverage single nucleus ATAC-seq to unveil cell-type specific signal for chromatin activity, microRNAs, super enhancers, and transcription factor networks (such as CREB1, AP-1 and ETV2) in FLC. The results provide the first high resolution map of chromatin features of FLC, which in turn affords the opportunity to study cell type specific transcriptional reprogramming in the FLC tumor microenvironment.