Imaging hematopoietic precursor division in real time
Imaging hematopoietic precursor division in real time
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DOI：
10.1016/j.stem.2007.08.009
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发表时间：
2007-11-01
期刊：
影响因子：
23.9
通讯作者：
Reya, Tannishtha
中科院分区：
文献类型：
--
作者：
Wu, Mingfu;Kwon, Hyog Young;Reya, Tannishtha
干细胞被认为通过不对称和对称分裂来平衡自我更新和分化，但这种分裂是否发生在造血发育过程中尚不清楚。使用Notch报告小鼠，其中GFP充当分化传感器，我们对造血前体进行成像，并显示它们经历对称和不对称分裂。此外，我们还表明，这些划分之间的平衡不是天生的，而是对外在和内在线索的反应。前分化环境中的前体以不对称分裂为主，而前更新环境中的前体以对称分裂为主。癌蛋白也可以影响分裂模式：尽管BCR-ABL主要改变分裂率和死亡率，但NUP98-HOXA9促进对称分裂，这表明不同的癌基因破坏了细胞功能的不同方面。这些研究建立了一个追踪造血前体分裂的系统，并表明对称和不对称分裂的平衡可以受到微环境的影响和癌基因的破坏。
Stem cells are thought to balance self-renewal and differentiation through asymmetric and symmetric divisions, but whether such divisions occur during hematopoietic development remains unknown. Using a Notch reporter mouse, in which GFP acts as a sensor for differentiation, we image hematopoietic precursors and show that they undergo both symmetric and asymmetric divisions. In addition we show that the balance between these divisions is not hardwired but responsive to extrinsic and intrinsic cues. Precursors in a prodifferentiation environment preferentially divide asymmetrically, whereas those in a prorenewal environment primarily divide symmetrically. Oncoproteins can also influence division pattern: although BCR-ABL predominantly alters the rate of division and death, NUP98-HOXA9 promotes symmetric division, suggesting that distinct oncogenes subvert different aspects of cellular function. These studies establish a system for tracking division of hematopoietic precursors and show that the balance of symmetric and asymmetric division can be influenced by the microenvironment and subverted by oncogenes.