In vivo imaging of haematopoietic cells emerging from the mouse aortic endothelium
In vivo imaging of haematopoietic cells emerging from the mouse aortic endothelium
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DOI：
10.1038/nature08764
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发表时间：
2010-03-04
期刊：
影响因子：
64.8
通讯作者：
Robin, Catherine
中科院分区：
文献类型：
--
作者：
Boisset, Jean-Charles;van Cappellen, Wiggert;Robin, Catherine
造血干细胞（HSC），负责成年小鼠的血液生产，首先在胚胎第10.5天（E10.5）开始在背主动脉中检测到（1-3）。对固定胚胎切片的免疫组织学分析揭示了造血细胞簇的存在，造血细胞簇附着于HSC可能定位的主动脉内皮（4-6）。HSC的起源长期以来一直存在争议，并且已经提出了几种直接HSC前体的候选者（参见参考文献7），包括具有造血潜力的特化内皮细胞群。在胚胎干细胞（ESC）培养系统中的体外（8，9）和通过内皮谱系追踪（5，10）和条件性缺失实验（11）的回顾性体内（11）中描述了这样的细胞。小鼠胚胎主动脉是否真的发生了从造血内皮细胞到HSC的转变尚不清楚，需要直接和实时的体内观察。为了解决这个问题，我们使用了延时共聚焦成像和一种新的解剖程序来可视化位于深处的主动脉。在这里，我们展示了直接从腹主动脉造血内皮细胞动态新生出现表型定义的HSC（Sca 1（+），c-kit（+），CD 41（+））。
Haematopoietic stem cells (HSCs), responsible for blood production in the adult mouse, are first detected in the dorsal aorta starting at embryonic day 10.5 (E10.5)(1-3). Immunohistological analysis of fixed embryo sections has revealed the presence of haematopoietic cell clusters attached to the aortic endothelium where HSCs might localize(4-6). The origin of HSCs has long been controversial and several candidates of the direct HSC precursors have been proposed (for review see ref. 7), including a specialized endothelial cell population with a haemogenic potential. Such cells have been described both in vitro in the embryonic stem cell (ESC) culture system(8,9) and retrospectively in vivo by endothelial lineage tracing(5,10) and conditional deletion experiments(11). Whether the transition from haemogenic endothelium to HSC actually occurs in the mouse embryonic aorta is still unclear and requires direct and real-time in vivo observation. To address this issue we used time-lapse confocal imaging and a new dissection procedure to visualize the deeply located aorta. Here we show the dynamic de novo emergence of phenotypically defined HSCs (Sca1(+), c-kit(+), CD41(+)) directly from ventral aortic haemogenic endothelial cells.