scRNA-seq demonstrates distinct transcriptomic changes with PRMT5 inhibitor resistance in the PDX MCL model. scRNA-seq was performed on PDX MCL splenic lymphocyte samples representing 3 different treatment conditions: (1) VC including parental, short-term, and long-term vehicle treated (n = 3); (2) short-term PRMT5 inhibitor–treated (treated 2 weeks before necropsy; n = 1); and (3) PRMT5-inhibitor–treated resistant (treated until ERC; n = 2). (A) Density UMAP plots demonstrating the transcriptional state change based on the treatment condition (VC, short-term treated, and resistant treated). (B) The Leiden method defines clusters of cells with shared transcriptional profiles independent of sample identity. (C) Differential abundance across Leiden clusters according to treatment status (resistant vs short-term treated). (D) Aggregated expression of indicated pathways according to Leiden cluster. (E) UMAP representation of mTOR differential expression in single cells.