Figure 6.
VEGF-C promotes BM EC proliferation and increases the expression of hematopoietic-regenerative factors after irradiation. (A) Experimental setup for evaluating the effects of Vegfc in the BM upon irradiation. Vegfc was deleted from the BM in 10-week-old Rosa26-CreERT2;Vegfcflox/flox mice using tamoxifen injections. VciΔR26 and Vcfl/fl mice received 4-Gy irradiation after a 2-week tamoxifen washout. Niche cells were isolated from irradiated (IR) VciΔR26 and Vcfl/fl mice and their nonirradiated (N-IR) controls 7 days after irradiation and analyzed using scRNA-seq. (B-C) UMAP plot showing the clustering of integrated nonhematopoietic BM stroma cells from IR VciΔR26 and Vcfl/fl mice and their N-IR controls. UMAP plot showing nonhematopoietic BM stroma cells from irradiated VciΔR26 and Vcfl/fl mice and their N-IR controls separately. Note that damaged ECs (green arrowhead) and Aqp1hi ECs (blue arrowhead) are increased after irradiation. (D) Percentages of the clusters (damaged ECs, Aqp1hi ECs, and Cxcl10 ECs) and quantification of ECs in S phase. (E) Dot plot showing selected differentially expressed genes in SECs (SEC-1, SEC-2, and Cxcl10 ECs), damaged ECs, Aqp1hi ECs, and AECs. Analysis of differentially expressed genes was performed between IR;Vcfl/fl vs N-IR;Vcfl/fl and IR;VciΔR26 vs N-IR;VciΔR26.

VEGF-C promotes BM EC proliferation and increases the expression of hematopoietic-regenerative factors after irradiation. (A) Experimental setup for evaluating the effects of Vegfc in the BM upon irradiation. Vegfc was deleted from the BM in 10-week-old Rosa26-CreERT2;Vegfcflox/flox mice using tamoxifen injections. VciΔR26 and Vcfl/fl mice received 4-Gy irradiation after a 2-week tamoxifen washout. Niche cells were isolated from irradiated (IR) VciΔR26 and Vcfl/fl mice and their nonirradiated (N-IR) controls 7 days after irradiation and analyzed using scRNA-seq. (B-C) UMAP plot showing the clustering of integrated nonhematopoietic BM stroma cells from IR VciΔR26 and Vcfl/fl mice and their N-IR controls. UMAP plot showing nonhematopoietic BM stroma cells from irradiated VciΔR26 and Vcfl/fl mice and their N-IR controls separately. Note that damaged ECs (green arrowhead) and Aqp1hi ECs (blue arrowhead) are increased after irradiation. (D) Percentages of the clusters (damaged ECs, Aqp1hi ECs, and Cxcl10 ECs) and quantification of ECs in S phase. (E) Dot plot showing selected differentially expressed genes in SECs (SEC-1, SEC-2, and Cxcl10 ECs), damaged ECs, Aqp1hi ECs, and AECs. Analysis of differentially expressed genes was performed between IR;Vcfl/fl vs N-IR;Vcfl/fl and IR;VciΔR26 vs N-IR;VciΔR26.

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