Continuous single-cell imaging of blood generation from haemogenic endothelium
Continuous single-cell imaging of blood generation from haemogenic endothelium
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DOI：
10.1038/nature07760
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发表时间：
2009-02-12
期刊：
影响因子：
64.8
通讯作者：
Schroeder, Timm
中科院分区：
文献类型：
--
作者：
Eilken, Hanna M.;Nishikawa, Shin-Ichi;Schroeder, Timm
尽管数十年的研究，在哺乳动物胚胎中产生第一个造血细胞的细胞的身份是未知的（1）。事实上，血细胞是否来自中胚层细胞、间充质祖细胞、双能内皮-造血前体细胞或造血内皮细胞仍然存在争议（2-9）。内皮细胞和血细胞在胚胎造血部位的接近性，以及它们相似的基因表达，导致了内皮细胞产生血液的假设。然而，由于缺乏技术（10），不可能在单细胞水平上连续观察血细胞的出现，并且假设存在造血内皮细胞仍然存在争议（1）。在这里，我们使用新的成像和细胞跟踪方法，表明胚胎内皮细胞可以造血。通过对产生内皮细胞和血集落的小鼠中胚层细胞的连续长期单细胞观察，有可能检测到产生血细胞的造血内皮细胞。通过同时检测形态学和多种分子和功能标志物来鉴定活的内皮细胞和造血细胞。新生血细胞与内皮细胞的分离与不对称细胞分裂没有直接联系，并且生血内皮细胞是从已经表达内皮标志物的细胞中指定的。这些结果提高了我们对哺乳动物血液的发育起源和胚胎干细胞产生造血干细胞的潜力的理解。
Despite decades of research, the identity of the cells generating the first haematopoietic cells in mammalian embryos is unknown(1). Indeed, whether blood cells arise from mesodermal cells, mesenchymal progenitors, bipotent endothelial - haematopoietic precursors or haemogenic endothelial cells remains controversial(2-9). Proximity of endothelial and blood cells at sites of embryonic haematopoiesis, as well as their similar gene expression, led to the hypothesis of the endothelium generating blood. However, owing to lacking technology(10) it has been impossible to observe blood cell emergence continuously at the single- cell level, and the postulated existence of haemogenic endothelial cells remains disputed(1). Here, using new imaging and cell- tracking methods, we show that embryonic endothelial cells can be haemogenic. By continuous long- term single- cell observation of mouse mesodermal cells generating endothelial cell and blood colonies, it was possible to detect haemogenic endothelial cells giving rise to blood cells. Living endothelial and haematopoietic cells were identified by simultaneous detection of morphology and multiple molecular and functional markers. Detachment of nascent blood cells from endothelium is not directly linked to asymmetric cell division, and haemogenic endothelial cells are specified from cells already expressing endothelial markers. These results improve our understanding of the developmental origin of mammalian blood and the potential generation of haematopoietic stem cells from embryonic stem cells.