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      HIF-2α - a mediator of stem cell altruism?

      , 1

      Stem Cell Research & Therapy

      BioMed Central

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          Abstract

          Human embryonic stem cells (hESCs) have been reported to confer cytoprotection in the context of tissue injury. This is somewhat counterintuitive given that microenvironmental factors such as hypoxia and oxidative stress may activate p53 and result in death and differentiation of these hESCs. In this article, we discuss a novel mechanism through which hESCs can be re-programmed (through exposure to hypoxia/oxidative stress) to transiently suppress p53, enhance 'stemness', and exist in a highly cytoprotective and undifferentiated state.

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          Most cited references 10

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          Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway.

          HIF plays a central role in the transcriptional response to changes in oxygen availability. The PHD family of oxygen-dependent prolyl hydroxylases plays a pivotal role in regulating HIF stability. The biochemical properties of these enzymes make them well suited to act as oxygen sensors. They also respond to other intracellular signals, including reactive oxygen species, nitric oxide, and certain metabolites, that can modulate the hypoxic response. HIF transcriptional activity is further tuned by FIH1-mediated asparagine hydroxylation. HIF affects signaling pathways that influence development, metabolism, inflammation, and integrative physiology. Accordingly, HIF-modulatory drugs are now being developed for diverse diseases.
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            Hypoxia and inflammation.

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              The role of oxygen availability in embryonic development and stem cell function.

               Brian Keith,  S. Simon (2008)
              Low levels of oxygen (O2) occur naturally in developing embryos. Cells respond to their hypoxic microenvironment by stimulating several hypoxia-inducible factors (and other molecules that mediate O2 homeostasis), which then coordinate the development of the blood, vasculature, placenta, nervous system and other organs. Furthermore, embryonic stem and progenitor cells frequently occupy hypoxic 'niches' and low O2 regulates their differentiation. Recent work has revealed an important link between factors that are involved in regulating stem and progenitor cell behaviour and hypoxia-inducible factors, which provides a molecular framework for the hypoxic control of differentiation and cell fate. These findings have important implications for the development of therapies for tissue regeneration and disease.
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                Author and article information

                Affiliations
                [1 ]School of Medicine and Medical Science, The Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland
                Contributors
                Journal
                Stem Cell Res Ther
                Stem Cell Res Ther
                Stem Cell Research & Therapy
                BioMed Central
                1757-6512
                2012
                18 December 2012
                18 December 2013
                : 3
                : 6
                : 52
                23253294 3580482 scrt143 10.1186/scrt143
                Copyright ©2012 BioMed Central Ltd
                Categories
                Commentary

                Molecular medicine

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