Wu Mingfu, Kwon Hyog Young, Rattis Frederique, Blum Jordan, Zhao Chen, Ashkenazi Rina, Jackson Trachette L, Gaiano Nicholas, Oliver Tim, Reya Tannishtha
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Cell Stem Cell. 2007 Nov;1(5):541-54. doi: 10.1016/j.stem.2007.08.009.
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.
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，但在造血发育过程中是否发生此类分裂仍不清楚。利用一种Notch报告基因小鼠（其中绿色荧光蛋白作为分化传感器），我们对造血前体细胞进行成像，并表明它们会经历对称和不对称分裂。此外，我们还表明，这些分裂之间的平衡并非固定不变，而是对外源和内在信号有反应。处于促分化环境中的前体细胞优先进行不对称分裂，而处于促更新环境中的前体细胞主要进行对称分裂。癌蛋白也可影响分裂模式：虽然BCR-ABL主要改变分裂速率和死亡率，但NUP98-HOXA9促进对称分裂，这表明不同的癌基因会破坏细胞功能的不同方面。这些研究建立了一个追踪造血前体细胞分裂的系统，并表明对称和不对称分裂的平衡可受微环境影响并被癌基因破坏。
