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Blood, 15 November 2004, Vol. 104, No. 10, pp. 3148-3152. Prepublished online as a Blood First Edition Paper on July 22, 2004; DOI 10.1182/blood-2004-03-0835.
Submitted March 4, 2004
Department of Human Genetics, Istituto di Genetica e Biofisica "Adriano Buzzati Traverso" CNR, Naples, Italy * Corresponding author; email: filosa{at}igb.cnr.it.
Glucose 6-phosphate dehydrogenase (G6PD) [EC 1.1.1.42] is an essential enzyme for rapid production of NADPH, as required upon exposure to oxidative stress. Mouse embryonic stem (ES) cells are competent for production of all embryonic and fetal/adult cell types. By studying the in vitro differentiation of embryonic bodies produced from G6pd deleted ES cells, that are totally unable to produce G6PD protein, we found that these are able to differentiate into mesodermal cells, cardiomyocytes, hepatocytes and primitive erythroid cells. However, we show here that, after the hemoglobin switch has taken place, definitive erythrocytes die by apoptosis. This apoptotic death is delayed by reducing agents and by a caspase inhibitor, but it is prevented only by restoring G6PD activity. Thus, G6PD proves indispensable for definitive erythropoiesis.
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