Extended Data Fig. 5: Related to Figs. 6, 7 and 8.
A) Transcription of iMSC-related genes in unstimulated MSC (blue), and MSC cultured in the supernatant of iMSC (green), with MSC-conditioned neutrophils (grey) or cultured with iMSC-conditioned neutrophils (orange). (i)MSC were generated from ADSC. Dotted lined depict paired samples (n = 5, collected over 3 experiments) B) Enrichment plots for the iMSC-signature (generated from DEGs of single cell RNA sequencing results in4), and iMSC-like cells signature (generated from data in Extended Data Fig. 3I) comparing MSC cultured with iMSC-conditioned neutrophils with MSC cultured in supernatant of iMSC C) Transcription of iMSC-related genes in unstimulated or IL-1β stimulated ADSC, or co-cultured with myeloma cell lines (n = 3, collected over 3 experiments) D) Transcription of SELP and E) PTGS2 in the non-hematopoietic compartment of controls and patients post-consolidation. F) Cluster distribution per patient in non-hematopoietic object. Colors represent clusters. ‘TMM’, treated MM-patient (post-consolidation). ‘CBM’, control G) Percentages of MSCs within the discrete MSC clusters per individual (n = 7 treated patients, and n = 6 controls) H) Percentage of MSC with a positive ‘iMSC-like cell’ score split by treatment-type and MRD-status after consolidation therapy (VTD, bortezomib, thalidomide, dexamethasone; D-VTD, daratumumab, bortezomib, thalidomide, dexamethasone; MRD, minimal residual disease)(n = 7 treated patients, and n = 6 controls) I) Transcription of IL6 and CXCL8 comparing non-cancer controls to patients after consolidation therapy in the non-hematopoietic object generated using Harmony (with sample ID, sex and sequencing batch as co-variates) J) Marker gene transcription in the 9 neutrophil clusters, split by condition (light green, controls; dark green, treated MM patients) K) Transcription of selected genes comparing clusters MatNeu2a and MatNeu2b to clusters MatNeu1 and ImmNeu in MM patients post consolidation L) Cluster distribution per patient in post-treatment neutrophil object. Colors represent clusters. ‘TMM’, treated MM-patient (post-consolidation). ‘CBM’, control. Data are presented as mean ± SEM. Significance was calculated in A using the Wald test (two-tailed) followed by a Benjamini–Hochberg correction, in B using pre-ranked geneset enrichment analysis (GSEA), and in H and G using the Mann–Whitney U test (two-tailed), ***P ≤ 0.001, ****P ≤ 0.0001, NS P > 0.05.
