Quantitative imaging of haematopoietic stem and progenitor cell localization and hypoxic status in the bone marrow microenvironment.
Quantitative imaging of haematopoietic stem and progenitor cell localization and hypoxic status in the bone marrow microenvironment.
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DOI：
10.1038/ncb2730
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发表时间：
2013-05
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
--
作者：
作为空间受限调控实体的造血干细胞生态位的存在依赖于这样一个概念，即造血干细胞和祖细胞(HSPC)处于独特的骨髓(BM)微环境中，具有明确的解剖和功能特征。在这里，我们利用一个强大的成像细胞仪平台，对HSPC在股骨BM腔中的分布进行全面的定量分析。我们发现HSPC优先定位于骨内区，在那里大多数与正弦和非正弦BM微血管密切相互作用，形成一个独特的循环系统。原位组织分析显示HSPC呈低氧状态，其特征是强滞留匹莫硝唑和表达HIF-1α，无论其在整个骨髓中的定位，与血管结构或细胞周期状态无关。这些研究认为，HSPC特有的低氧状态不仅仅是微氧生态位的结果，而且可能部分受到细胞特异性机制的调节。
The existence of a hematopoietic stem cell niche as a spatially confined regulatory entity relies on the notion that hematopoietic stem and progenitor cells (HSPCs) are strategically positioned in unique bone marrow (BM) 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 BM cavities of femoral bones. We find that HSPCs preferentially localize in endosteal zones, where the majority closely interacts with sinusoidal and non-sinusoidal BM 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 BM, 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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影响因子：
23.9
作者：
Butler JM;Nolan DJ;Vertes EL;Varnum-Finney B;Kobayashi H;Hooper AT;Seandel M;Shido K;White IA;Kobayashi M;Witte L;May C;Shawber C;Kimura Y;Kitajewski J;Rosenwaks Z;Bernstein ID;Rafii S
通讯作者：
Rafii S
影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ
影响因子：
32.4
作者：
Omatsu, Yoshiki;Sugiyama, Tatsuki;Nagasawa, Takashi
通讯作者：
Nagasawa, Takashi
影响因子：
3.5
作者：
Piccoli, Claudia;D'Aprile, Annamaria;Capitanio, Nazzareno
通讯作者：
Capitanio, Nazzareno
影响因子：
3.7
作者：
Kimura Y;Ding B;Imai N;Nolan DJ;Butler JM;Rafii S
通讯作者：
Rafii S