AK2is an adenylate phosphotransferase that localizes at the intermembrane spaces of the mitochondria,and its mutations cause a severe combined immunodeficiency with neutrophil maturation arrest namedreticular dysgenesis (RD). Although the dysfunction of hematopoietic stem cells (HSCs) has beenimplicated, earlier developmental events that affect the fate of HSCs and/or hematopoietic progenitorshave not been reported. Here, we used RD-patient-derived induced pluripotent stem cells (iPSCs) as amodel of AK2-deficient human cells. Hematopoietic differentiation from RD-iPSCs was profoundlyimpaired. RD-iPSC-derived hemoangiogenic progenitor cells (HAPCs) showed decreased ATP distributionin the nucleus and altered global transcriptional profiles. Thus, AK2 has a stage-specific role in main-taining the ATP supply to the nucleus during hematopoietic differentiation, which affects the tran-scriptional profiles necessary for controlling the fate of multipotential HAPCs. Our data suggest thatmaintaining the appropriate energy level of each organelle by the intracellular redistribution of ATP isimportant for controlling the fate of progenitor cells.