Concise Review: Genetic Dissection of Hypoxia Signaling Pathways in Normal and Leukemic Stem Cells
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- Deniz Gezer
- MRC Centre for Regenerative Medicine. University of Edinburgh, Edinburgh, United Kingdom
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- Milica Vukovic
- MRC Centre for Regenerative Medicine. University of Edinburgh, Edinburgh, United Kingdom
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- Tomoyoshi Soga
- Institute for Advanced Biosciences Keio University, Mizukami, Tsuruoka, Yamagata, Japan
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- Patrick J. Pollard
- Cancer Biology and Metabolism Group Institute of Genetics and Molecular Medicine University of Edinburgh, Edinburgh, United Kingdom
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- Kamil R. Kranc
- MRC Centre for Regenerative Medicine. University of Edinburgh, Edinburgh, United Kingdom
説明
<jats:title>Abstract</jats:title> <jats:p>Adult hematopoiesis depends on rare multipotent hematopoietic stem cells (HSCs) that self-renew and give rise to progenitor cells, which differentiate to all blood lineages. The strict regulation of the fine balance between self-renewal and differentiation is essential for normal hematopoiesis and suppression of leukemia development. HSCs and progenitor cells are commonly assumed to reside within the hypoxic BM microenvironment, however, there is no direct evidence supporting this notion. Nevertheless, HSCs and progenitors do exhibit a hypoxic profile and strongly express Hif-1α. Although hypoxia signaling pathways are thought to play important roles in adult HSC maintenance and leukemogenesis, the precise function of Hif-dependent signaling in HSCs remains to be uncovered. Here we discuss recent gain-of-function and loss-of-function studies that shed light on the complex roles of hypoxia-signaling pathways in HSCs and their niches in normal and malignant hematopoiesis. Importantly, we comment on the current and often contrasting interpretations of the role of Hif-dependent signaling in stem cell functions. Stem Cells 2014;32:1390–1397</jats:p>
収録刊行物
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- Stem Cells
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Stem Cells 32 (6), 1390-1397, 2014-05-23
Oxford University Press (OUP)
