Fig. 5: Fate mapping of perturbed hematopoiesis.

a–c Fgd5^{ZsGreen:CreERT2}/R26^LSL-tdRFP mice were TAM-induced, treated with 5-FU (n = 5) or left untreated (n = 5), sacrificed at 35 days after treatment, and bone marrow populations and peripheral blood leukocytes were analyzed for RFP expression. b Ratios of peripheral blood cell numbers in treated (5-FU) vs. untreated (untr.) animals 6 days after treatment (means and SD are shown). c Label in populations 35 days after treatment is shown as percentage of RFP⁺ cells in ES HSC (left graph) or normalized as fraction of label in ES HSC (right graph, mean with SEM, one-way ANOVA with Sidak correction). d–g Fgd5^{ZsGreen:CreERT2}/R26^LSL-tdRFP mice were TAM-induced, treated with romiplostim (n = 4) or saline (NaCl, n = 4), and sacrificed 11 d after start of treatment and hematopoietic populations were analyzed for RFP expression. e Time-course of platelet numbers (means and SD are shown). f RFP labeling in ES HSCs (means and SEM are shown). g Label in bone marrow and blood populations is shown as fraction of label in ES HSC in respective populations (mean with SEM, one-way ANOVA with Sidak correction). h Graphical overview of altered cell fluxes (number of cells differentiated per day) by romiplostim application. Orange arrows represent >10× upregulated cell fluxes. Gray arrows indicate minor or non-significant changes. (cf. Supplementary Fig. 11). i Inferred ratio of cell fluxes via CD48^−/lo MkP to cell fluxes via CD48^hi MkP at steady state (NaCl, gray) or after romiplostim (orange) perturbation. j Cell fluxes from CD201^−/lo Sca-1^lo HSCs into Sca-1^lo MPPs and CD48^–/lo MkPs at steady state (NaCl, gray) or after romiplostim (orange) perturbation. In i and j, the error bars represent 95% confidence bounds.