Fig. 7: BM ECs promote hematopoietic regeneration via secretion of R spondin 2.
From: Neuropilin 1 regulates bone marrow vascular regeneration and hematopoietic reconstitution
a IPA of functions and diseases enriched in BM ECs at 72 h following 500 cGy and treatment with anti-NRP1 relative to irradiated control BM ECs. p values shown for pair-wise comparisons and each replicate is a pool of sorted BM ECs (n = 5 mice). b Heat map of genes that encode secreted proteins expressed ≥ 2-fold in BM ECs from irradiated mice treated with anti-NRP1 compared to BM ECs from irradiated controls. Each replicate is a pool of sorted BM ECs from five mice. c R spondin 2 (RSPO2) ELISA of supernatants from BM ECs following 800 cGy irradiation and culture with 10 µg/ml anti-NRP1 or IgG (n = 3–5/group; p = 0.0034). d PB WBC and NEU at day +10 following 500 cGy in mice treated with anti-NRP1, 10 µg anti-R spondin 2, anti-NRP1 + anti-R spondin 2, or IgG every other day × 10 days (n = 5–7 mice/group; WBC: p = 0.015, NEU: p = 0.0135). Dotted lines represent levels in non-IRR controls. e (Left) Flow cytometry of BM KSL cells and CD150+CD41/48-KSL LT-HSCs in mice at day +10 following 500 cGy and treatment with anti-NRP1, anti-R spondin 2, anti-NRP1 + anti-R spondin 2, or IgG. Numbers represent percentages in each gate; (Right) % BM KSL and % SLAM KSL cells in each treatment group (n = 5–7 mice/group; KSL: p = 0.007; SLAM KSL: p = 0.0123). f Numbers of BM KSL and SLAM HSCs from mice at day +10 following 500 cGy and treatment with anti-NRP1, anti-R spondin 2, anti-NRP1 + anti-R spondin 2, or IgG (n = 5–7/group; KSL: p = 0.0067; SLAM KSL: p = 0.0013). g Total BM CFCs and CFU-GEMMs in mice at day +10 following 500 cGy and treatments as shown (n = 5/group; CFCs: p = 0.0002; GEMM: p = 0.0026). h Numbers of CFU-GEMMs from BM c-kit+lin− cells at day +3 following 300 cGy and treatment with 100 ng/ml Wnt3a, 200 ng/ml R spondin 2, or the combination (n = 3–5/group; p < 0.0001). c–g Two-way ANOVA followed by two-sided Holm-Sidak unpaired t-tests; h One-way ANOVA with Holm-Sidak’s multiple comparison two-sided t-test. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Source Data file provided.
