Arteriolar niches maintain haematopoietic stem cell quiescence.
Arteriolar niches maintain haematopoietic stem cell quiescence.
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细胞周期静止是造血干细胞维持的重要特征。虽然各种候选基质细胞已被确定为潜在的HSC龛，静止的HSC在骨髓（BM）中的空间定位仍然不清楚。在这里，使用一种新的方法，结合整体安装共聚焦免疫荧光成像技术和计算建模来分析血管结构，基质细胞和HSC之间的显着的三维关联，我们表明，静止的HSC与小动脉，优先发现在骨内膜BM。这些小动脉仅被罕见的NG2+周细胞覆盖，与窦状隙相关的LepR+细胞不同。HSC细胞周期的药理学或遗传激活改变了HSC从NG2+动脉周围小生境到LepR+窦周围小生境的分布。NG2+细胞的条件性耗竭诱导HSC循环并减少BM中功能性长期再增殖的HSC。因此，这些结果表明，小动脉龛是必不可少的，以维持HSC的静止。
Cell cycle quiescence is a critical feature contributing to haematopoietic stem cell (HSC) maintenance. Although various candidate stromal cells have been identified as potential HSC niches, the spatial localization of quiescent HSCs in the bone marrow (BM) remains unclear. Here, using a novel approach that combines whole-mount confocal immunofluorescence imaging techniques and computational modelling to analyse significant tridimensional associations among vascular structures, stromal cells and HSCs, we show that quiescent HSCs associate specifically with small arterioles that are preferentially found in endosteal BM. These arterioles are ensheathed exclusively by rare NG2+ pericytes, distinct from sinusoid-associated LepR+ cells. Pharmacological or genetic activation of HSC cell cycle alters the distribution of HSCs from NG2+ peri-arteriolar niches to LepR+ peri-sinusoidal niches. Conditional depletion of NG2+ cells induces HSC cycling and reduces functional long-term repopulating HSCs in BM. These results thus indicate that arteriolar niches are indispensable to maintain HSC quiescence.
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影响因子：
64.5
作者：
Hsu YC;Pasolli HA;Fuchs E
通讯作者：
Fuchs E
影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ
DOI：
10.1126/science.1180794
发表时间：
2010-01-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Li L;Clevers H
通讯作者：
Clevers H
DOI：
10.1073/pnas.1434429100
发表时间：
2003-09-16
影响因子：
11.1
作者：
Chi, JT;Chang, HY;Brown, PO
通讯作者：
Brown, PO
影响因子：
64.8
作者：
通讯作者：
--