The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
HIF-2α regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth
Open accessAbstract
The division, differentiation, and function of stem cells and multipotent progenitors are influenced by complex signals in the microenvironment, including oxygen availability. Using a genetic “knock-in” strategy, we demonstrate that targeted replacement of the oxygen-regulated transcription factor HIF-1α with HIF-2α results in expanded expression of HIF-2α-specific target genes including Oct-4, a transcription factor essential for maintaining stem cell pluripotency. We show that HIF-2α, but not HIF-1α, binds to the Oct-4 promoter and induces Oct-4 expression and transcriptional activity, thereby contributing to impaired development in homozygous Hif-2 α KI/KI embryos, defective hematopoietic stem cell differentiation in embryoid bodies, and large embryonic stem cell (ES)-derived tumors characterized by altered cellular differentiation. Furthermore, loss of HIF-2α severely reduces the number of embryonic primordial germ cells, which require Oct-4 expression for survival and/or maintenance. These results identify Oct-4 as a HIF-2α-specific target gene and indicate that HIF-2α can regulate stem cell function and/or differentiation through activation of Oct-4, which in turn contributes to HIF-2α's tumor promoting activity.
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Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180
Cellular and developmental control of O 2 homeostasis by hypoxia-inducible factor 1α
Iyer, N. V., Kotch, L. E., Agani, F., Leung, S. W., Laughner, E., Wenger, R. H., Gassmann, M., Gearhart, J. D., Lawler, A. M., Yu, A. Y., et al. (1998) · Genes & Development · doi:10.1101/gad.12.2.149 · Cited by 2,476
Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation
Hu, C.-J., Wang, L.-Y., Chodosh, L. A., Keith, B., & Simon, M. C. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.24.9361-9374.2003 · Cited by 1,386
Self-citationEma, M., Taya, S., Yokotani, N., Sogawa, K., Matsuda, Y., & Fujii-Kuriyama, Y. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4273 · Cited by 1,016
Raval, R. R., Lau, K. W., Tran, M. G. B., Sowter, H. M., Mandriota, S. J., Li, J.-L., Pugh, C. W., Maxwell, P. H., Harris, A. L., & Ratcliffe, P. J. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.13.5675-5686.2005 · Cited by 940
Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein
Kondo, K., Klco, J., Nakamura, E., Lechpammer, M., & Kaelin, W. G. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00043-0 · Cited by 761
Inhibition of HIF2α Is Sufficient to Suppress pVHL-Defective Tumor Growth
Kondo, K., Kim, W. Y., Lechpammer, M., & Kaelin, W. G. (2003) · PLoS Biology · doi:10.1371/journal.pbio.0000083 · Cited by 611
Jögi, A., Øra, I., Nilsson, H., Lindeheim, Å., Makino, Y., Poellinger, L., Axelson, H., & Påhlman, S. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.102660199 · Cited by 399
Oxygen-Regulated Gene Expression in Bovine Blastocysts1
Harvey, A. J., Kind, K. L., Pantaleon, M., Armstrong, D. T., & Thompson, J. G. (2004) · Biology of Reproduction · doi:10.1095/biolreprod.104.028639 · Cited by 189
Cited by
Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway.
Kaelin, W. G., & Ratcliffe, P. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.04.009 · Cited by 3,251
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-citationHypoxia signalling in cancer and approaches to enforce tumour regression
Pouysségur, J., Dayan, F., & Mazure, N. M. (2006) · Nature · doi:10.1038/nature04871 · Cited by 1,676
Hypoxia-Inducible Factor-1 (HIF-1)
Ke, Q., & Costa, M. (2006) · Molecular Pharmacology · doi:10.1124/mol.106.027029 · Cited by 1,646
Oxygen in Stem Cell Biology: A Critical Component of the Stem Cell Niche
Mohyeldin, A., Garzón-Muvdi, T., & Quiñones-Hinojosa, A. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.07.007 · Cited by 1,535
Metadata
- Authors
- Covello, K. L., Kehler, J., Yu, H., Gordan, J. D., Arsham, A. M., Hu, C.-J., Labosky, P. A., Simon, M. C., & Keith, B.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2006-03-01
- Volume
- 20
- Issue
- 5
- Pages
- 557-570
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2105925116
- Cited by
- 821
- References
- 11
- Type
- posted content
- Language
- en
- Open access
- diamond
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- CoChat. (2026). Citation check: HIF-2α regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth. https://app.cochat.ai/papers/10.1101/gad.1399906
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- Covello, K. L., Kehler, J., Yu, H., Gordan, J. D., Arsham, A. M., Hu, C.-J., Labosky, P. A., Simon, M. C., & Keith, B. (2006). HIF-2α regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth. Genes & Development. https://doi.org/10.1101/gad.1399906
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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