Fig. 5: Meningeal fibroblast-derived BMP ligands signal to metastatic tumour cells.
a–c, Chord diagram (top) and schematic diagram (bottom) demonstrating the BMP signalling interactions from meningeal fibroblasts to the microenvironment of non-tumour leptomeninges (LPT-WT) (a), low leptomeningeal metastatic burden (low LPT-MET) (b) and high leptomeningeal metastatic burden (high LPT-MET) samples (c), with BMPR1A_R2 denoted as 1A_R2 and BMPR1B_R2 denoted as 1B_R2. d, Violin plots showing Bmp5, Bmp4 and Bmp7 expression in meningeal fibroblasts from LPT-WT, low LPT-MET and high LPT-MET scRNA-seq samples. e,f, Ptch-SB spinal cord with metastasis (LPT-MET) and primary tumour cross-sections fluorescently labelled with GFP, ERTR7, DAPI and BMP4 (e) or BMP7 (f). The proportion of tumour cells (GFP+) and microenvironment cells (GFP−DAPI+) close to BMP4-positive signal (n = 14 and n = 15 images for LPT-MET and primary, respectively) (e) and BMP7-positive signal (n = 13 and n = 8 images for LPT-MET and primary, respectively) (f) was quantified per field of view. g, Ptch-SB spinal cord LPT-MET and primary tumour cross-sections fluorescently labelled with GFP, pSMAD1/5 and ERTR7. The pSMAD and GFP double-positive cells normalized to total GFP volume were quantified in LPT-MET samples and primary tumour core and boundary regions per field of view (n = 37, 10 and 9 images for LPT-MET, core and boundary, respectively). P values were generated using two-tailed unpaired t-test with Welch’s correction, the centre line represents the mean and error bars represent the standard deviation, *P < 0.0001. Scale bars, 120 µm (e–g). h, Box plots showing Id1 and Id2 mean expression per sample in primary tumour (n = 4 mice) and LPT-MET tumour cells (n = 4 mice) from the scRNA-seq data. The centre line represents the median (50% percentile), the hinges represent 25% and 75% percentiles, and the whiskers represent the 1.5 interquartile range. P values were generated using a two-tailed Student’s t-test.
