Extended Data Fig. 7: Key role of IL-1 in the aging of both BM niche and blood system.
a, b, GSEA results in old Il1r1−/− HSPC population for the Gene Ontology pathways affected in either old WT HSPCs (a) or young WT HSPCs (b) identified by droplet-based scRNAseq analyses. n/a, non-available; ns, not significant; *nominal p value ≤ 0.05, ** nominal p value ≤ 0.01, *** nominal p value ≤ 0.001. c, Peripheral blood CD45.1+ donor chimerism (left) and number of donor-derived GMPs (right) in young or old WT and Il1r1−/− CD45.2+ recipient mice at 4 months (mo) after lethal irradiation and transplantation (Tplx) with 2 × 106 young WT CD45.1+ donor BM cells. d, Il1r1 expression in the droplet-based scRNAseq of young and old WT stroma and LK/LSK datasets. Cells in the UMAP were colored according to the expression levels of the indicated genes. Color scheme is based on ln scale of normalized counts from the indicated minimum (gray) to maximum (red) value in the scale. e–i, Unchanged aging features in old Tnf−/− mice with: (e) color scheme; (f) blood parameters; (g) endosteal (left) and central marrow (right) mesenchymal population frequencies; (h) BM hematopoietic population frequencies; and (i) engraftment over time (left) and lineage reconstitution (right) at 4 mo post-Tplx of the indicated HSC populations. Results are from 3 independent cohorts of young and old WT and age-matched Tnf−/− mice, with HSCs isolated from the pooled BM of mice of the same genotype and transplanted into 3 to 5 recipients, each. Data are means ± S.D. except for engraftment results shown in (i) (± S.E.M.); P-values were obtained by Kolmogorov-Smirnov test (a,b), by one-way Anova adjusted for multiple comparisons using the Holm-Šídák method (c,i), or by two-tailed Student’s t-test without adjustment for multiple comparisons (f, g, h).
