Fig. 1: Longitudinal scRNA-seq of MCL during treatment.

a Schematic view of the experimental design to delineate therapeutic resistance of MCL. The discovery cohort included scRNA-seq and deep whole-exome sequencing (WES) of MCL cells collected longitudinally from three responders (Rs) and two nonresponders (NRs), together with normal PBMCs from two healthy donors. The genomic and immune correlates of response identified from the discovery cohort were then cross-validated by multiple platforms including bulk RNA-seq, WES, and flow cytometry of independent patient cohorts, scRNA-seq of patient-derived PDX models, as well as in vitro and in vivo functional studies using MCL patient-derived cell lines. b Coronal or axial images from CT scans pre-ibrutinib treatment (baseline) and post-treatment (disease progression) (left). Spleen sizes were measured and labeled with schematics of treatment and sample collection time points for scRNA-seq (middle); as well as the kinetics of white blood cell (WBC) counts during the course of treatment (right). Specimens were collected at multiple time points before and during the treatment when feasible, including pretreatment, on-treatment, and progression samples. c A t-SNE overview of the cells that passed quality control. Each dot of the t-SNE (t-distributed stochastic neighbor embedding) plot represents a single cell. Cells are color-coded by subject (MCL patients B–E, V, and healthy donors N1/N2, cells are merged as N), ibrutinib response status (NR: non-responder; R: responder), and by the cell type. d Cell composition dynamics at different time points during sample collection.