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Hypoxia Pathway Proteins in Normal and Malignant Hematopoiesis
The regulation of oxygen (O₂) levels is crucial in embryogenesis and adult life, as O₂ controls a multitude of key cellular functions. Low oxygen levels (hypoxia) are relevant for tissue physiology as they are integral to adequate metabolism regulation and cell fate. Hence, the hypoxia response is o...
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Published in: | Cells (Basel, Switzerland) Switzerland), 2019-02, Vol.8 (2), p.155 |
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description | The regulation of oxygen (O₂) levels is crucial in embryogenesis and adult life, as O₂ controls a multitude of key cellular functions. Low oxygen levels (hypoxia) are relevant for tissue physiology as they are integral to adequate metabolism regulation and cell fate. Hence, the hypoxia response is of utmost importance for cell, organ and organism function and is dependent on the hypoxia-inducible factor (HIF) pathway. HIF pathway activity is strictly regulated by the family of oxygen-sensitive HIF prolyl hydroxylase domain (PHD) proteins. Physiologic hypoxia is a hallmark of the hematopoietic stem cell (HSC) niche in the bone marrow. This niche facilitates HSC quiescence and survival. The present review focuses on current knowledge and the many open questions regarding the impact of PHDs/HIFs and other proteins of the hypoxia pathway on the HSC niche and on normal and malignant hematopoiesis. |
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Low oxygen levels (hypoxia) are relevant for tissue physiology as they are integral to adequate metabolism regulation and cell fate. Hence, the hypoxia response is of utmost importance for cell, organ and organism function and is dependent on the hypoxia-inducible factor (HIF) pathway. HIF pathway activity is strictly regulated by the family of oxygen-sensitive HIF prolyl hydroxylase domain (PHD) proteins. Physiologic hypoxia is a hallmark of the hematopoietic stem cell (HSC) niche in the bone marrow. This niche facilitates HSC quiescence and survival. The present review focuses on current knowledge and the many open questions regarding the impact of PHDs/HIFs and other proteins of the hypoxia pathway on the HSC niche and on normal and malignant hematopoiesis.</description><identifier>ISSN: 2073-4409</identifier><identifier>EISSN: 2073-4409</identifier><identifier>DOI: 10.3390/cells8020155</identifier><identifier>PMID: 30781787</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Animals ; Blood ; Bone marrow ; Bone Marrow - pathology ; Cell fate ; Embryogenesis ; Enzymes ; Genes ; Hematopoiesis ; Hematopoietic stem cells ; Hematopoietic Stem Cells - metabolism ; HIF ; Homeostasis ; Humans ; Hydroxylase ; Hypoxia ; Hypoxia - pathology ; Hypoxia-inducible factors ; Kinases ; leukemia ; Metabolism ; Metabolites ; Oxygen ; oxygen sensors ; Physiology ; Prolyl hydroxylase ; Proteins ; Review ; Signal Transduction ; Stem Cell Niche ; Stem cells</subject><ispartof>Cells (Basel, Switzerland), 2019-02, Vol.8 (2), p.155</ispartof><rights>2019 by the authors. 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subjects | Animals Blood Bone marrow Bone Marrow - pathology Cell fate Embryogenesis Enzymes Genes Hematopoiesis Hematopoietic stem cells Hematopoietic Stem Cells - metabolism HIF Homeostasis Humans Hydroxylase Hypoxia Hypoxia - pathology Hypoxia-inducible factors Kinases leukemia Metabolism Metabolites Oxygen oxygen sensors Physiology Prolyl hydroxylase Proteins Review Signal Transduction Stem Cell Niche Stem cells |
title | Hypoxia Pathway Proteins in Normal and Malignant Hematopoiesis |
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