Fig. 4: ME7-infected mice exhibit HSC senescence during aging.
Levels of mitochondrial ROS (A) and SA-β-gal activity (B) in PrPC-negative and -positive BM HSCs from control and ME7-infected old-aged mice were measured (n = 7). Levels of p16 (C) and phospho-p38 (D) in PrPC-negative and -positive BM HSCs from both old-aged mouse groups were analyzed after cells had been fixed and permeabilized (n > 6). E For analysis of competitive repopulation capacity, PrPC-negative or PrPC-positive LSK cells from control or ME7-infected old-aged mice (CD45.2) were co-transplanted with equal numbers (5 × 103) of PrPC-negative or PrPC-positive LSK cells from competitor mice (CD45.1) and accessory cells (1 × 106) from the PB of non-conditioned recipient mice (CD45.1/2) into conditioned recipient mice (CD45.1/2, 900 rads). F The CD45.1/CD45.2 ratio in PB collected from recipient mice at 4 months post-transplantation was evaluated by flow cytometry (n = 5). G The survival rate was measured in recipient mice (CD45.1/2) that had been transplanted with CD45.2-expressing BM cells (5 × 105) from primary recipient mice, which had been transplanted with LSK cells (n = 10). Donor cells were able to support recipient animal survival for 4–5 weeks because of short-term repopulating cells (i.e., radioprotective capacity); survival beyond 16 weeks requires long-term repopulating cells. All data are presented as means ± SDs. *p < 0.05, **p < 0.01, and ***p < 0.001 vs. control, as determined by Student’s t test.
