Stromal ECM profile is deeply modified in lymphoma-invaded BM. (A) Scatter plot of upregulated pathways in MSC_Gr.Late vs MSC_Sh (y-axis) and MSC_Gr.Early vs MSC_Sh (x-axis) as determined by gene set enrichment analysis (Hallmarks, Canonical pathways, and Gene Ontology databases). Pathways specific to each comparison are color coded: red for MSC_Gr.Late vs MSC_Sh, blue for MSC_Gr.Early vs MSC_Sh, and black for common pathways. ECM-related pathways are indicated by a star. (B) Heat map of the top 100 genes upregulated in at least 1 of the following comparisons: MSC_Gr.Late vs MSC_Gr.Early; MSC_Gr.Late vs MSC_Sh; and MSC_Early vs MSC_Sh. (C) Immunofluorescence on BM sections of sham (CA) or grafted (CB) mouse femurs for Sparc (red), collagen VI (ColVI; green), and human CD20 (hCD20; cyan; upper panel). Nuclei were counterstained with DAPI (blue); scale bars, 50 μm. Box (i) in Gr.Late femur indicates the area magnified below for Sparc, ColVI, and CD20 staining (scale bars, 50 μm). Immunofluorescence on BM sections of sham (CA) or grafted (CB) mouse femurs for Lox (red), and hCD20 (cyan; lower panel). Nuclei were counterstained with DAPI (blue); scale bars, 50 μm. (D) Compass-score differential activity of metabolic subsystems between MSC_Gr.Early vs MSC_Late (y-axis) and MSC_Gr.Early vs MSC_Sh (x-axis). Cohens d medians are calculated for each subsystem of Recon 2 pathways by taking each Cohens d value obtained for each reaction of this subsystem. Subsystems are categorized in global metabolic pathways and names of subsystems belonging to the “glycan metabolism” category are given in detail. (E) UMAP plot of non-endothelial stromal cells from human metastasis-free mesenteric LNs (MFLNs) and human FL LNs colored by sample origin (blue, MFLNs, and red, FL LNs; left). Visualization of the MSC_Gr. ECM and collagen signature scores derived from the 100 genes upregulated in MSC_Gr.Late and/or MSC_Gr.Early in MFLN vs FL stromal cells (right). (F) UMAP plot of scores from lymphoma matrisome signatures previously defined from DLBCL LNs30 and solid cancer CAF signatures previously defined from pancreatic cancers31 and from breast cancers32 were plotted on the LepR+ MSC clusters. iCAF, inflammatory CAF.

Stromal ECM profile is deeply modified in lymphoma-invaded BM. (A) Scatter plot of upregulated pathways in MSC_Gr.Late vs MSC_Sh (y-axis) and MSC_Gr.Early vs MSC_Sh (x-axis) as determined by gene set enrichment analysis (Hallmarks, Canonical pathways, and Gene Ontology databases). Pathways specific to each comparison are color coded: red for MSC_Gr.Late vs MSC_Sh, blue for MSC_Gr.Early vs MSC_Sh, and black for common pathways. ECM-related pathways are indicated by a star. (B) Heat map of the top 100 genes upregulated in at least 1 of the following comparisons: MSC_Gr.Late vs MSC_Gr.Early; MSC_Gr.Late vs MSC_Sh; and MSC_Early vs MSC_Sh. (C) Immunofluorescence on BM sections of sham (CA) or grafted (CB) mouse femurs for Sparc (red), collagen VI (ColVI; green), and human CD20 (hCD20; cyan; upper panel). Nuclei were counterstained with DAPI (blue); scale bars, 50 μm. Box (i) in Gr.Late femur indicates the area magnified below for Sparc, ColVI, and CD20 staining (scale bars, 50 μm). Immunofluorescence on BM sections of sham (CA) or grafted (CB) mouse femurs for Lox (red), and hCD20 (cyan; lower panel). Nuclei were counterstained with DAPI (blue); scale bars, 50 μm. (D) Compass-score differential activity of metabolic subsystems between MSC_Gr.Early vs MSC_Late (y-axis) and MSC_Gr.Early vs MSC_Sh (x-axis). Cohens d medians are calculated for each subsystem of Recon 2 pathways by taking each Cohens d value obtained for each reaction of this subsystem. Subsystems are categorized in global metabolic pathways and names of subsystems belonging to the “glycan metabolism” category are given in detail. (E) UMAP plot of non-endothelial stromal cells from human metastasis-free mesenteric LNs (MFLNs) and human FL LNs colored by sample origin (blue, MFLNs, and red, FL LNs; left). Visualization of the MSC_Gr. ECM and collagen signature scores derived from the 100 genes upregulated in MSC_Gr.Late and/or MSC_Gr.Early in MFLN vs FL stromal cells (right). (F) UMAP plot of scores from lymphoma matrisome signatures previously defined from DLBCL LNs30 and solid cancer CAF signatures previously defined from pancreatic cancers31 and from breast cancers32 were plotted on the LepR+ MSC clusters. iCAF, inflammatory CAF.

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