Division of Transfusion Medicine, Department of Laboratory Medicine, Children's Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Nat Cell Biol. 2013 May;15(5):533-43. doi: 10.1038/ncb2730. Epub 2013 Apr 28.
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.
造血干细胞龛作为一个空间限定的调节实体的存在依赖于这样一种观点，即造血干细胞和祖细胞（HSPCs）被战略性地定位于具有特定解剖和功能特征的独特骨髓微环境中。在这里，我们采用强大的成像细胞计量学平台对股骨骨髓腔中的 HSPC 分布进行全面定量分析。我们发现 HSPCs 优先定位于骨内膜区，在那里它们与窦状和非窦状骨髓微血管最密切地相互作用，形成一个独特的循环系统。原位组织分析表明，无论在骨髓中的定位、邻近血管结构还是细胞周期状态如何，HSPCs 都表现出缺氧特征，这由强烈保留匹莫硝唑和 HIF-1α 的表达来定义。这些研究表明，HSPCs 的特征性缺氧状态不仅仅是由于缺氧微环境的结果，而可能部分受到细胞特异性机制的调节。
