Low HSC numbers are sufficient to meet acutely increased demand for mature blood cells. (A) HSC-CreERT/R26^DTA/DTA mice (n = 4-7 per group) were TAM-treated (2 × 0.2 mg/g BW) and 12 weeks later injected with PHZ or saline. PB hematocrit (HCT) was measured directly before PHZ injection and 3 and 6 days afterward (middle). One week after PHZ injection, BM populations from 2 femora were quantified by flow cytometry (right). Mean ± SD, absolute counts from 2 femora were normalized to the mean of saline-treated Cre⁻ controls (dotted line). (B) HSC-CreERT/R26^DTA/DTA animals were TAM-treated (2 × 0.1 mg/g BW) and 19 weeks later i.p. injected with antiplatelet serum. Platelet (PLT) counts in PB were measured at the indicated time points before and after platelet depletion. HSC and progenitor populations in the BM were analyzed 6 days after PLT depletion (PLT-depl). Mean ± SD, absolute counts from 2 femora, normalized to the mean of Cre⁻ controls (dotted line). (C) HSC-CreERT/R26^DTA/DTA mice (n = 4-5 per group) were TAM-induced and 10 weeks later injected with G-CSF or saline. PB was analyzed 1 day after the last injection for immunophenotypic LT-HSCs (middle). Two weeks after G-CSF treatment BM populations from 2 femora were quantified by flow cytometry (right, normalization and display as in panel A). (D) HSC-CreERT⁺R26^DTA/DTA (Cre⁺, n = 3-5) and control mice (Cre⁻, n = 4-9) were TAM-induced (2 × 0.2 mg/g BW) and 13 weeks later injected IV with 5-FU or saline. PB WBC counts of 5-FU–treated mice were determined at the indicated time points (middle data plot, means ± SD, Cre⁺, red; Cre⁻, dotted black line). BM populations of HSC-CreERT⁺R26^DTA/DTA and Cre⁻ control mice were measured 13 days after 5-FU injection. Means ± SD are shown; absolute counts from 2 femora were normalized to the mean of 5-FU–treated Cre⁻ controls. For data of saline-treated controls, refer to supplemental Figure 5E. Ctrl, control; MkP, megakaryocyte progenitor; Pre MegE (see Pronk et al³²  for description); Pro Ery, proerythroblast.