Suppression of VGCC abrogates increased mitochondrial activity and largely rescues HSC defects in Twist1-deficient mice. (A) Schematic overview of the cilnidipine treatment of irradiated mice. Control (Ctrl) and cKO mice were injected with cilnidipine (1 mg/kg per dose; intraperitoneal injection) for 7 consecutive days after IR treatment. (B-D) The concentrations of intracellular Ca²⁺ (B), mitochondrial Ca²⁺ (C), and ROS level (D) in BM LT-HSCs from cKO and Ctrl mice treated with cilnidipine or vehicle after IR treatment (n = 4-6; Student t test). (E) Kaplan-Meier survival curves of cKO and Ctrl mice administered cilnidipine or vehicle after IR at 7 Gy (n = 8-10; log-rank test). (F-G) Frequencies (F) and cell-cycle analysis (G) of BM LT-HSCs from cKO and Ctrl mice treated with cilnidipine or vehicle after IR treatment (n = 4-6; Student t test). (H) Kaplan-Meier survival curves of cKO and Ctrl mice administered cilnidipine or vehicle after serial 5-FU injection (n = 6-9; log-rank test). (I-J) Frequencies (I) and cell-cycle analysis (J) of BM LT-HSCs from cKO and Ctrl mice treated with cilnidipine or vehicle (n = 4-5; Student t test). Data are shown as means ± standard deviation. *P < .05, ***P < .001. MFI, mean fluorescence intensity; ns, not significant.