Figure 1.

VEGF-C regulates the integrity of the BM LepR⁺ HSC niche. (A) Relative Vegfc mRNA level in sorted WT PECAM-1⁺ ECs and LepR⁺ stromal cells, analyzed by qPCR (normalized to WBM; n = 2 mice per group). (B) Experimental outline of scRNA-seq analysis of LepR⁺ cells and VE-cadherin–positive ECs from Lepr-Cre;tdTomato BM. (C) UMAP plots of BM LepR-tdTomato–positive cells and VE-cadherin–positive ECs (left). A feature plot shows Lepr and Cdh5 expression (right). (D) A feature plot showing Vegfc, Flt4 (VEGFR-3), and Kdr (VEGFR-2) expression. (E) Experimental setup for evaluating the effects of Vegfc deletion in the BM. Vegfc was deleted from adult BM by administering 5 daily tamoxifen injections to 7- to 10-week-old Rosa26-CreER^T2;Vegfc^flox/flox mice. (F) Representative confocal immunofluorescence images of femur sections from Vc^iΔR26 and Vc^fl/fl mice 5 months after deletion. Staining for ECs (endomucin, green) and perivascular cells (LepR, red), with quantification (right) (n = 5-6 mice per group). Bar represents 50 μm. (G) Quantification of HSPC subsets per femur from 7-month-old Vc^iΔR26 mice and Vc^fl/fl littermate controls, determined by CD48 and CD150 staining (n = 13-14 mice per group). Quantification of HSPC subsets per femur from 22- to 23-month-old Vc^iΔR26 mice and Vc^fl/fl littermate controls (n = 6 male mice per group). Values show mean ± SD. Statistical significance was determined with the 2-tailed, unpaired Student t test. MPP, multipotential progenitor. *P < .05; **P < .01.