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

被引:0
作者
César Nombela-Arrieta
Gregory Pivarnik
Beatrice Winkel
Kimberly J. Canty
Brendan Harley
John E. Mahoney
Shin-Young Park
Jiayun Lu
Alexei Protopopov
Leslie E. Silberstein
机构
[1] Children’s Hospital Boston,Division of Transfusion Medicine, Department of Laboratory Medicine
[2] University of Illinois,Department for Chemical and Biomolecular Engineering
[3] Dana-Farber Cancer Institute,Division of Hematologic Malignancies
[4] Present address: Institute for Applied Cancer Science,undefined
[5] The University of Texas MD Anderson Cancer Center,undefined
[6] Texas 77030,undefined
[7] USA,undefined
来源
Nature Cell Biology | 2013年 / 15卷
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摘要
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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页码:533 / 543
页数:10
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