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Quantitative imaging of haematopoietic stem and progenitor cell localization and hypoxic status in the bone marrow microenvironment
Open accessAbstract
The existence of a haematopoietic stem cell niche as a spatially confined regulatory entity relies on the notion that haematopoietic stem and progenitor cells (HSPCs) are strategically positioned in unique bone marrow microenvironments with defined anatomical and functional features. Here, we employ a powerful imaging cytometry platform to perform a comprehensive quantitative analysis of HSPC distribution in bone marrow cavities of femoral bones. We find that HSPCs preferentially localize in endosteal zones, where most closely interact with sinusoidal and non-sinusoidal bone marrow microvessels, which form a distinctive circulatory system. In situ tissue analysis reveals that HSPCs exhibit a hypoxic profile, defined by strong retention of pimonidazole and expression of HIF- 1α, regardless of localization throughout the bone marrow, adjacency to vascular structures or cell-cycle status. These studies argue that the characteristic hypoxic state of HSPCs is not solely the result of a minimally oxygenated niche but may be partially regulated by cell-specific mechanisms.
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Cites
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Metabolic Regulation of Hematopoietic Stem Cells in the Hypoxic Niche
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Oxygen, a source of life and stress
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Cited by
The bone marrow niche for haematopoietic stem cells
Morrison, S. J., & Scadden, D. T. (2014) · Nature · doi:10.1038/nature12984 · Cited by 2,451
Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone
Kusumbe, A. P., Ramasamy, S. K., & Adams, R. H. (2014) · Nature · doi:10.1038/nature13145 · Cited by 2,155
Direct measurement of local oxygen concentration in the bone marrow of live animals
Spencer, J. A., Ferraro, F., Roussakis, E., Klein, A., Wu, J., Runnels, J. M., Zaher, W., Mortensen, L. J., Alt, C., Turcotte, R., et al. (2014) · Nature · doi:10.1038/nature13034 · Cited by 1,167
Metabolic requirements for the maintenance of self-renewing stem cells
Ito, K., & Suda, T. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3772 · Cited by 1,014
Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs
Phinney, D. G., Di Giuseppe, M., Njah, J., Sala, E., Shiva, S., St Croix, C. M., Stolz, D. B., Watkins, S. C., Di, Y. P., Leikauf, G. D., et al. (2015) · Nature Communications · doi:10.1038/ncomms9472 · Cited by 1,007
Metadata
- Authors
- Nombela-Arrieta, C., Pivarnik, G., Winkel, B., Canty, K. J., Harley, B., Mahoney, J. E., Park, S.-Y., Lu, J., Protopopov, A., & Silberstein, L. E.
- Venue
- Nature Cell Biology
- Published
- 2013-04-28
- Volume
- 15
- Issue
- 5
- Pages
- 533-543
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2093570808
- Cited by
- 551
- References
- 6
- FWCI
- 38.61
- Type
- journal article
- Language
- en
- Open access
- green
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- Nombela-Arrieta, C., Pivarnik, G., Winkel, B., Canty, K. J., Harley, B., Mahoney, J. E., Park, S.-Y., Lu, J., Protopopov, A., & Silberstein, L. E. (2013). Quantitative imaging of haematopoietic stem and progenitor cell localization and hypoxic status in the bone marrow microenvironment. Nature Cell Biology. https://doi.org/10.1038/ncb2730
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