Extended Data Fig. 5: Down-regulated genes upon PSGL-1 treatment tend to be repressed upon aged HSCs transplanted to young recipients.
From: Aberrant engagement of P-selectin drives hematopoietic stem cell aging in mice
(a) DEGs in SelpKO HSCs upon PSGL-1 treatment. Volcano plot showing distribution of the false discovery rate (FDR) (-log10FDR) and the fold changes (logFC). Up-regulated and down-regulated genes are indicated in red and blue, respectively (FDR < 0.05). (b) Correlation analyses of Post-TXP down-regulated genes with IL6 activating genes using single-cell expression data from GSE70657 ref. 40, GSE59114 ref. 41 and GSE232022 ref. 13, respectively. Values on x and y axis are the enrichment scores of the gene sets in single cell. Correlation analyses using Pearson coefficient R and linear regression t-test, P < 2.2 × 10−16 for all correlation. Gene sets can be found in Supplementary Tables 1 and 2. Linear regression line and 95% confidence interval is presented. (c) Venn diagram showing overlapping genes between down-regulated genes upon transplantation and PSGL-1 exposure. 15 common genes are depicted under the diagram. (d-e) Correlation analyses of genes repressed by PSGL-1 with Post-TXP down-regulated genes and up-regulated HSC aging signature genes27 using single-cell expression data from GSE70657 ref. 40 (d) (Post−TXP_down, P < 1.3 × 10−05; HSC_Aging_up, P = 0.02) and GSE59114 ref. 41 (e) (Post−TXP_down, P < 9.5 × 10−14; HSC_Aging_up, P = 6.4 × 10−11). Values on x and y axis are the enrichment scores of the gene sets in single cell. Correlation analyses using Pearson coefficient R and linear regression t-test. Gene sets can be found in Supplementary Tables 1–3. Linear regression line and 95% confidence interval is presented. (f) Gating strategy of P-selectin+ cells from LSK fraction of HPC7 cells. (g-h) Phophoflow analysis for p-ERK1/2, p-STAT3 and p-p38 of LSK P-selectin+ HPC7 cells with or without PSGL-1 treatment for 15 minutes (upper panel) or 1 hour (lower panel) with (h) or without (g) Selpin. Bar plot shows MFI fold changes (n = 3). **P = 0.004, *P = 0.0116, two-tailed t-test. Data are presented as mean values +/− SD.
