Single-cell mapping of alternative splicing linked to checkpoint immunotherapy response.

ABSTRACT: Evidence suggests that alternative RNA splicing (AS) plays a critical role in tumor biology and may contribute to the generation of tumor antigens. Here, we develop a method to detect AS in short-read single-cell 5'-RNA-sequencing data, allowing us to uniquely characterize the heterogeneity and dynamic changes in AS in individual cell types within the tumor microenvironment. We identify numerous splicing events specific to either cancer cells or stromal cell types or for triple-negative versus estrogen receptor-positive breast cancers (BCs). By correlating these splice events with expression of splicing regulators in individual cells, we also identify their potential mediators. For instance, we identify and functionally validate the Epithelial Splicing Regulatory Protein-1 (ESRP1) to drive

SUBMITTER: Xiong J 

PROVIDER: S-EPMC12631129 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature