Dataset Information
Increased expression of HIF2? during iron deficiency-associated megakaryocytic differentiation.
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ABSTRACT: Background
Iron deficiency is associated with reactive thrombocytosis; however, the mechanisms driving this phenomenon remain unclear. We previously demonstrated that this occurs alongside enhanced megakaryopoiesis in iron-deficient rats, without alterations in the megakaryopoietic growth factors thrombopoietin, interleukin-6, or interleukin-11.Objectives
The aim of this study was to evaluate megakaryocyte differentiation under iron deficiency in an in vitro model and to investigate potential genes involved in this process.Methods
Human erythroleukemia and megakaryoblastic leukemia cell lines, as well as cord-blood derived hematopoietic stem cells were cultured under iron deficiency. Cell morphology, ploidy, expression of CD41, CD61, and CD42b, and proplatelet formation were assessed in iron-deficient cultures. Polymerase chain reaction arrays were used to identify candidate genes that were verified using real-time polymerase chain reaction. Hypoxia-inducible factor 1, ? subunit (HIF2?) protein expression was assessed in bone marrow sections from iron-deficient rats and vascular endothelial growth factor (VEGF)-A in culture supernatants.Results and conclusions
Iron deficiency enhanced megakaryoid features in cell lines, increasing ploidy and initiating formation of proplatelet-like structures. In cord blood cell cultures, iron deficiency increased the percentage of cells expressing megakaryopoietic markers and enhanced proplatelet formation. HIF2? and VEGF were identified as potential pathways involved in this process. HIF2? protein expression was increased in megakaryocytes from iron-deficient rats, and VEGF-A concentration was higher in iron-deficient culture supernatants. Addition of VEGF-A to cell cultures increased percentage expression of megakaryocyte CD41. In conclusion, the data demonstrate that iron deficiency augments megakaryocytic differentiation and proplatelet formation and a potential role of HIF2? in megakaryopoiesis.
SUBMITTER: Jimenez K
PROVIDER: S-EPMC4949661 | biostudies-literature | 2015 Jun
REPOSITORIES: biostudies-literature
Publications
Increased expression of HIF2α during iron deficiency-associated megakaryocytic differentiation.
Journal of thrombosis and haemostasis : JTH 20150423 6
<h4>Background</h4>Iron deficiency is associated with reactive thrombocytosis; however, the mechanisms driving this phenomenon remain unclear. We previously demonstrated that this occurs alongside enhanced megakaryopoiesis in iron-deficient rats, without alterations in the megakaryopoietic growth factors thrombopoietin, interleukin-6, or interleukin-11.<h4>Objectives</h4>The aim of this study was to evaluate megakaryocyte differentiation under iron deficiency in an in vitro model and to investig ...[more]