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. 2022 May 12;17(6):1428–1441. doi: 10.1016/j.stemcr.2022.04.009

Figure 7.

Figure 7

Inhibition of PDH or ROS restores eIF2α-Atf4 ISR signaling in HSCs of irradiated WT mice

(A–G) WT mice were irradiated with X-rays, 1.75 Gy weekly × 4, and treated with vehicle (Veh), CPI-613, or NAC. LSK cells were collected from mouse BM 1 month after the last IR. LSKs isolated from irradiated Ripk3−/− mice were studied as controls. OCR (A), mtROS (B), OPA cleavage (C), p-eIF2a (D), ATF4 expression (E), rate of protein synthesis (F), and senescence (G) were examined.

(H) BM MNCs were collected 1 week after the last IR and transplanted into lethally irradiated mice. Recipient mice were monitored for leukemia development. Survival curves for the mice were plotted by Kaplan-Meier graphing. Data in (B), (D), (F), and (G) show one of the three biological triplicate experiments. ∗∗p < 0.01, compared with respective vehicle controls.