Fig. 3: Meningeal fibroblasts are recruited and undergo proliferation in the presence of tumour cells. | Nature Cell Biology

Fig. 3: Meningeal fibroblasts are recruited and undergo proliferation in the presence of tumour cells.

From: Metastatic medulloblastoma remodels the local leptomeningeal microenvironment to promote further metastatic colonization and growth

Fig. 3

a, Whole-mount spinal leptomeninges from Pdgfra-H2BeGFP/NSG mice implanted with MB813–mCherry and D458–mCherry cells into the lateral ventricle and fluorescently labelled with GFP+ fibroblasts, mCherry (MB813 tumour), Ki67 and DAPI. The proportion of PDGFRα and Ki67 double-positive cells in control (sham injection) and MB813 and D458 (tumour low and high regions) samples was quantified per field of view (n = 10, 8, 13, 9 and 12 images for control, MB813 low, MB813, D458 low and D458, respectively). b, A chord diagram of scRNA-seq data highlighting the signalling pathways from Ptch-SB metastatic tumour cells to the meningeal fibroblasts. c, A schematic representation of the experimental design with D458 cells overexpressing PDGFA and signalling to PDGFRα+ meningeal fibroblasts (far left). Whole-mount spinal leptomeninges fluorescently labelled with GFP+ fibroblasts, BFP+ tumour and Ki67 from Pdgfra-H2BeGFP/NSG mice implanted with D458 cells expressing control BFP and PDGFA-BFP into the lateral ventricle. The total PDGFRα+ cells and proportion of PDGFRα and Ki67 double-positive cells were quantified per field of view (n = 14 and n = 10 images for control BFP and PDGFA-BFP, respectively). d, Quantifications from whole-mount spinal leptomeninges of NSG mice implanted with D458 GFP-Luc control-BFP and D458 GFP-Luc PDGFA-BFP into the lateral ventricle and fluorescently labelled with Ki67. The total number of Ki67+ GFP+ tumour cells was normalized to the total GFP+ tumour volume per field of view (n = 10 images per group). e, Kaplan–Meier survival analysis from NSG mice implanted with D458 GFP-Luc control-BFP (n = 7 mice) and D458 GFP-Luc PDGFA-BFP (n = 7 mice) into the lateral ventricle (log-rank (Mantel–Cox) test was performed). P values were generated from two-tailed unpaired t-test with Welch’s correction, the centre line represents mean and the error bars represent the standard deviation for a, c and d. n.s., not significant (P = 0.3166). Scale bars, 120 µm (a and c).

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