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Quantitative imaging of haematopoietic stem and progenitor cell localization and hypoxic status in the bone marrow microenvironment

2013; Nature Portfolio; Volume: 15; Issue: 5 Linguagem: Inglês

10.1038/ncb2730

1476-4679

César Nombela‐Arrieta, Gregory Pivarnik, Beatrice Winkel, Kimberly J. Canty, Brendan A.C. Harley, John E. Mahoney, Shin‐Young Park, Jiayun Lu, Alexei Protopopov, Leslie E. Silberstein,

Mesenchymal stem cell research

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. Haematopoietic stem and progenitor cells (HSPCs) are found in unique bone marrow microenvironments. Silberstein and colleagues use imaging cytometry to quantitatively determine HSPC distribution in femoral bones. They find that HSPCs are in endosteal zones, in close proximity to specialized microvessels, and that they appear in a hypoxic state whether or not they are close to the vasculature.