The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
O2 regulates stem cells through Wnt/β-catenin signalling
Open accessAbstract
Stem cells reside in specialized microenvironments or 'niches' that regulate their function. In vitro studies using hypoxic culture conditions (< 5% O2) have revealed strong regulatory links between O2 availability and functions of stem and precursor cells. Although some stem cells are perivascular, others may occupy hypoxic niches and be regulated by O2 gradients. However, the underlying mechanisms remain unclear. Here, we show that hypoxia inducible factor-1α (HIF-1α), a principal mediator of hypoxic adaptations, modulates Wnt/β-catenin signalling in hypoxic embryonic stem (ES) cells by enhancing β-catenin activation and expression of the downstream effectors LEF-1 and TCF-1. This regulation extends to primary cells, including isolated neural stem cells (NSCs), and is not observed in differentiated cells. In vivo, Wnt/β-catenin activity is closely associated with low O2 regions in the subgranular zone of the hippocampus, a key NSC niche. Hif-1α deletion impairs hippocampal Wnt-dependent processes, including NSC proliferation, differentiation and neuronal maturation. This decline correlates with reduced Wnt/β-catenin signalling in the subgranular zone. O2 availability, therefore, may have a direct role in stem cell regulation through HIF-1α modulation of Wnt/β-catenin signalling.
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Cites
Wnt signalling in stem cells and cancer
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XTcf-3 Transcription Factor Mediates β-Catenin-Induced Axis Formation in Xenopus Embryos
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HIF‐1α is required for solid tumor formation and embryonic vascularization
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Self-citationWnt signalling regulates adult hippocampal neurogenesis
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Hypoxia requires Notch signaling to maintain the undifferentiated cell state
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A specialized vascular niche for adult neural stem cells
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Cited by
HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression
Keith, B., Johnson, R. S., & Simon, M. C. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3183 · Cited by 1,693
Self-citationThe many faces and functions of β‐catenin
Valenta, T., Hausmann, G., & Basler, K. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.150 · Cited by 1,598
Metabolic Regulation of Hematopoietic Stem Cells in the Hypoxic Niche
Suda, T., Takubo, K., & Semenza, G. L. (2011) · Cell Stem Cell · doi:10.1016/j.stem.2011.09.010 · Cited by 844
TCF/LEFs and Wnt Signaling in the Nucleus
Cadigan, K. M., & Waterman, M. L. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a007906 · Cited by 760
Regulation of Immunity and Inflammation by Hypoxia in Immunological Niches
Taylor, C. T., & Colgan, S. P. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.103 · Cited by 713
Metadata
- Authors
- Mazumdar, J., O'Brien, W. T., Johnson, R. S., LaManna, J. C., Chavez, J. C., Klein, P. S., & Simon, M. C.
- Venue
- Nature Cell Biology
- Published
- 2010-09-19
- Volume
- 12
- Issue
- 10
- Pages
- 1007-1013
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W1968461724
- Cited by
- 454
- References
- 34
- FWCI
- 17.49
- Type
- journal article
- Language
- en
- Open access
- green
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