In Vitro Erythropoiesis at Different pO<sub>2</sub> Induces Adaptations That Are Independent of Prior Systemic Exposure to Hypoxia
Greta Simionato,
Antonia Rabe,
Joan Sebastián Gallego-Murillo,
Carmen van der Zwaan,
Arie Johan Hoogendijk,
Maartje van den Biggelaar,
Giampaolo Minetti,
Anna Bogdanova,
Heimo Mairbäurl,
Christian Wagner,
Lars Kaestner,
Emile van den Akker
Affiliations
Greta Simionato
Department of Experimental Physics, University Campus, Building E2.6, Saarland University, 66123 Saarbrücken, Germany
Antonia Rabe
Department of Experimental Physics, University Campus, Building E2.6, Saarland University, 66123 Saarbrücken, Germany
Joan Sebastián Gallego-Murillo
Sanquin Research, Landsteiner Laboratory, Department of Hematopoiesis, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The Netherlands
Carmen van der Zwaan
Sanquin Research, Landsteiner Laboratory, Department of Molecular Hematology, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The Netherlands
Arie Johan Hoogendijk
Sanquin Research, Landsteiner Laboratory, Department of Molecular Hematology, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The Netherlands
Maartje van den Biggelaar
Sanquin Research, Landsteiner Laboratory, Department of Molecular Hematology, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The Netherlands
Giampaolo Minetti
Department of Biology and Biotechnology “L. Spallanzani”, Laboratories of Biochemistry, University of Pavia, I-27100 Pavia, Italy
Anna Bogdanova
Red Blood Cell Research Group, Institute of Veterinary Physiology, University of Zurich, CH-8057 Zurich, Switzerland
Heimo Mairbäurl
University Hospital Heidelberg, Medical Clinic VII, Sports Medicine, 69120 Heidelberg, Germany
Christian Wagner
Department of Experimental Physics, University Campus, Building E2.6, Saarland University, 66123 Saarbrücken, Germany
Lars Kaestner
Department of Experimental Physics, University Campus, Building E2.6, Saarland University, 66123 Saarbrücken, Germany
Emile van den Akker
Sanquin Research, Landsteiner Laboratory, Department of Hematopoiesis, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The Netherlands
Hypoxia is associated with increased erythropoietin (EPO) release to drive erythropoiesis. At high altitude, EPO levels first increase and then decrease, although erythropoiesis remains elevated at a stable level. The roles of hypoxia and related EPO adjustments are not fully understood, which has contributed to the formulation of the theory of neocytolysis. We aimed to evaluate the role of oxygen exclusively on erythropoiesis, comparing in vitro erythroid differentiation performed at atmospheric oxygen, a lower oxygen concentration (three percent oxygen) and with cultures of erythroid precursors isolated from peripheral blood after a 19-day sojourn at high altitude (3450 m). Results highlight an accelerated erythroid maturation at low oxygen and more concave morphology of reticulocytes. No differences in deformability were observed in the formed reticulocytes in the tested conditions. Moreover, hematopoietic stem and progenitor cells isolated from blood affected by hypoxia at high altitude did not result in different erythroid development, suggesting no retention of a high-altitude signature but rather an immediate adaptation to oxygen concentration. This adaptation was observed during in vitro erythropoiesis at three percent oxygen by a significantly increased glycolytic metabolic profile. These hypoxia-induced effects on in vitro erythropoiesis fail to provide an intrinsic explanation of the concept of neocytolysis.
