AI Article Synopsis
- AK2 is a key enzyme in mitochondria, and mutations in this enzyme lead to a severe condition called reticular dysgenesis, which affects the immune system and neutrophil development.
- Research using stem cells from RD patients showed that hematopoietic differentiation was significantly impaired, indicating problems at the very early stages of cell development.
- The study found that AK2 is crucial for providing energy (ATP) to the nucleus during the differentiation process, which influences the genetic activity needed for the proper development of blood stem cells.
Article Abstract
AK2 is an adenylate phosphotransferase that localizes at the intermembrane spaces of the mitochondria, and its mutations cause a severe combined immunodeficiency with neutrophil maturation arrest named reticular dysgenesis (RD). Although the dysfunction of hematopoietic stem cells (HSCs) has been implicated, earlier developmental events that affect the fate of HSCs and/or hematopoietic progenitors have not been reported. Here, we used RD-patient-derived induced pluripotent stem cells (iPSCs) as a model of AK2-deficient human cells. Hematopoietic differentiation from RD-iPSCs was profoundly impaired. RD-iPSC-derived hemoangiogenic progenitor cells (HAPCs) showed decreased ATP distribution in the nucleus and altered global transcriptional profiles. Thus, AK2 has a stage-specific role in maintaining the ATP supply to the nucleus during hematopoietic differentiation, which affects the transcriptional profiles necessary for controlling the fate of multipotential HAPCs. Our data suggest that maintaining the appropriate energy level of each organelle by the intracellular redistribution of ATP is important for controlling the fate of progenitor cells.
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| http://dx.doi.org/10.1016/j.bbrc.2018.02.139 | DOI Listing |
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