Deficiency of Antioxidative Paraoxonase 2 (Pon2) Leads to Increased Number of Phenotypic LT-HSCs and Disturbed Erythropoiesis

Figure 5

PON2 deficiency causes oxidative stress, but does not impair but rather improve HSC function. (a) L-012 chemiluminescence signal of freshly isolated BMCs from young WT and Pon2^-/- mice quantified over time for ROS formation (representative graph); . , , , ns: not significant vs. WT; two-tailed unpaired -test. (b) Total ROS level in LT-HSCs, ST-HSCs, and MPPs of young (2-3 months) WT and Pon2^-/- mice stained with cell-specific markers (LT-HSCs: Lin^-, Sca¹⁺, ckit⁺, CD135^-, and CD150⁺; ST-HSCs: Lin^-, Sca¹⁺, ckit⁺, CD135^-, and CD150^-; MPPs: Lin^-, Sca¹⁺, ckit⁺, CD135⁺, and CD150^-) and H₂DCF-DA, analyzed by FACS (); . , ns: not significant vs. WT; two-tailed unpaired -test (representative histograms showing the DCF-DA data comparing WT and Pon2^-/- mice, see Figure S6). BMCs isolated from young WT and Pon2^-/- mice stained with cell-specific markers for (c) LT-HSCs or (d) ST-HSCs and annexin V for quantification of apoptotic cells (). Box and whiskers; whiskers: 10-90 percentile; , ns: not significant vs. WT; two-tailed unpaired -test. (e) Experimental scheme for competitive bone marrow transplantation. (f) Percentage of CD45.2-positive cells in the blood of competitive transplanted young mice 3, 7, 11, 15, 19, and 22 weeks after transplantation (); . , , , ns: not significant; two-tailed unpaired -test.

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