The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Expansion of human SCID-repopulating cells under hypoxic conditions
Open accessAbstract
It has been proposed that bone marrow (BM) hematopoietic stem and progenitor cells are distributed along an oxygen (O2) gradient, where stem cells reside in the most hypoxic areas and proliferating progenitors are found in O2-rich areas. However, the effects of hypoxia on human hematopoietic stem cells (HSCs) have not been characterized. Our objective was to evaluate the functional and molecular responses of human BM progenitors and stem cells to hypoxic conditions. BM lineage-negative (Lin-) CD34+CD38- cells were cultured in serum-free medium under 1.5% O2 (hypoxia) or 20% O2 (normoxia) for 4 days. Using limiting dilution analysis, we demonstrate that the absolute number of SCID-repopulating cells (SRCs) increased by 5.8-fold in hypoxic cultures compared with normoxia, and by 4.2-fold compared with freshly isolated Lin-CD34+CD38- cells. The observed increase in BM-repopulating activity was associated with a preferential expansion of Lin-CD34+CD38- cells. We also demonstrate that, in response to hypoxia, hypoxia-inducible factor-1alpha protein was stabilized, surface expression of angiogenic receptors was upregulated, and VEGF secretion increased in BM Lin-CD34+ cultures. The use of low O2 levels to enhance the survival and/or self-renewal of human BM HSCs in vitro represents an important advance and could have valuable clinical implications.
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Hypoxia — a key regulatory factor in tumour growth
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HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing
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Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1
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Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours
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Cited by
Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells
Li, Z., Bao, S., Wu, Q., Wang, H., Eyler, C., Sathornsumetee, S., Shi, Q., Cao, Y., Lathia, J., McLendon, R. E., et al. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.03.018 · Cited by 1,354
Hypoxia-Inducible Factors, Stem Cells, and Cancer
Keith, B., & Simon, M. C. (2007) · Cell · doi:10.1016/j.cell.2007.04.019 · Cited by 1,179
Self-citationSimsek, T., Kocabas, F., Zheng, J., DeBerardinis, R. J., Mahmoud, A. I., Olson, E. N., Schneider, J. W., Zhang, C. C., & Sadek, H. A. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.07.011 · Cited by 1,101
Regulation of the HIF-1α Level Is Essential for Hematopoietic Stem Cells
Takubo, K., Goda, N., Yamada, W., Iriuchishima, H., Ikeda, E., Kubota, Y., Shima, H., Johnson, R. S., Hirao, A., Suematsu, M., et al. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.06.020 · Cited by 891
Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia
Parmar, K., Mauch, P., Vergilio, J.-A., Sackstein, R., & Down, J. D. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701152104 · Cited by 867
Metadata
- Authors
- Danet, G. H., Pan, Y., Luongo, J. L., Bonnet, D. A., & Simon, M. C.
- Venue
- Journal of Clinical Investigation
- Published
- 2003-07-01
- Volume
- 112
- Issue
- 1
- Pages
- 126-135
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2061217297
- Cited by
- 345
- References
- 9
- FWCI
- 6.62
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Danet, G. H., Pan, Y., Luongo, J. L., Bonnet, D. A., & Simon, M. C. (2003). Expansion of human SCID-repopulating cells under hypoxic conditions. Journal of Clinical Investigation. https://doi.org/10.1172/jci17669
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