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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Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2019-02, Vol.8 (2), p.155
Main Authors: Wielockx, Ben, Grinenko, Tatyana, Mirtschink, Peter, Chavakis, Triantafyllos
Format: Article
Language:English
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
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Summary: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.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells8020155