Single-cell epigenomic profiling of H3K27ac reveals the dynamic changes of B cell driving inflammation-cancer transition
TL;DR
This study established an integrative strategy enabling high confidence cell identity assignment in sparse epigenomic data, and revealed the roles of B cell subtypes in the regulation of tumor immunity.
Abstract
Transcriptomic and epigenomic analyses at the single-cell level are critical for demonstrating the composition and regulatory network within the tumor microenvironment. Though single-cell ATAC-seq is widely-used, it is insufficient to fully interpret the functional connections. Here, we performed scRNA-seq and H3K27ac MobiChIP profiling in an AOM/DSS-induced colorectal cancer model, and developed an AI-assisted workflow for single-cell epigenomic and transcriptomic integrative analyses. Our results reveal Lrrk2+ B cells, one new subset of naïve B cells, are enriched during inflammation and suppresses CD4+/CD8+ T cell function via IL-7/IL-12. Epigenetic priming in Lrrk2+ B cells at the inflammation stage enables activation of NF-κB target genes at the cancer stage, driving inflammation-to-cancer transition. Pharmacological LRRK2 inhibition abrogated Lrrk2+ B cells and attenuated tumorigenesis. Our study established an integrative strategy enabling high confidence cell identity assignment in sparse epigenomic data, and revealed the roles of B cell subtypes in the regulation of tumor immunity.