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. 2021 May 17;12:2877. doi: 10.1038/s41467-021-22872-z

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© The Author(s) 2021, corrected publication 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — a Color-coded t-SNE plots of the malignant B cells. Color-coded cell representation by subject (Responders: C, D, V; non-responders: B; and healthy donors: N1, N2), sample collection time, and by cell cycle stage. b Transcriptomic heterogeneity and evolution of cancer hallmarks associated with ibrutinib resistance. From the Molecular Signature Database (MSigDB), 50 hallmark cancer gene sets were downloaded, and a pathway activity score was calculated for each single cell. The top 13 cancer hallmark pathways upregulated in the progressive sample are shown. c Heatmap representation of differentially expressed genes (representative ones) from five selected pathways across cell sub-populations B0, B1, B4a, and B4b from patient B compared to normal samples (N). d Schematic view of the establishment of B4-derived PDX model and experimental strategy of sample collection for scRNA-seq analysis. e Developmental trajectories representation of malignant cell populations from patient B (B0, B1, B4a, and B4b) and B4-derived PDX tumors along inferred pseudotime by Monocle2. Each point corresponds to a single cell; all points are color-coded according to the inferred pseudotime. Monocle 2 was run with default parameters on the hallmark gene sets (OXPHOS and mTORC1 signaling) downloaded from MSigDB. f tSNE Plots featuring CKD4, MKI67, BIRC3, NFKB2 and RELB genes expression in cells from patient B tumor and B4-derived PDX tumors.