Extended Data Fig. 4: Age-related changes in blood and BM populations and altered lineage bias in old MPPs.
a, Overlap between cytokines upregulated in old BM fluids and published SASP profile40. b, Representative SA-β-gal staining in control irradiated mouse embryonic fibroblasts (MEF) and isolated young and old MSC-S and OLC. Representative of 3 independent experiments. Scale bar, 20 µm. c, Absolute expression of Il1b in different mature hematopoietic cell types and unfractionated endosteal and central marrow stroma from pooled young and old samples. Results are expressed as -log(dCt) relative to gapdh. d, Complete blood count (CBC) parameters in young and old mice. Results are from 7 independent cohorts. WBC, white blood cell; My, myeloid; Ly, lymphocyte; RBC, red blood cell; Pt, platelet. e, Cellularity and quantification of mature populations in young and old BM. Results are from 3 independent cohorts. Gr, granulocyte. f, Quantification of progenitor populations in young and old BM. Results are from 3 independent cohorts. CMP, common myeloid progenitor; GMP, granulocyte-macrophage progenitor; MEP, megakaryocyte-erythrocyte progenitor; CLP, common lymphoid progenitor; CFU-E, erythroid colony-forming unit; Pre-GM, pre-granulocyte/macrophage; Pre-MegE, pre-megakaryocyte/erythrocyte; MkP, megakaryocyte progenitor. g, Representative staining and quantification of young and old HSC markers. Results are from 2 independent cohorts, with data represented as box and whiskers (min to max) and expressed as fold changes in mean fluorescence intensity (MFI) relative to young HSCs. h, Characteristic expression patterns of lineage determinant genes in the droplet-based scRNAseq young and old LK/LSK dataset. Cells in the UMAP were colored according to the expression levels of the indicated genes. i, IPA Upstream Regulators analysis of young and old populations from the droplet-based scRNAseq young and old LK/LSK dataset filtered on cytokines and growth factors. Data are means ± S.D. except for (g) where box ranges from 25th to 75th percentile with center line at the median, and whiskers range from minima to maxima; P-values were obtained by two-tailed Welch’s t-test without adjustment for multiple comparisons.
