Science：CBF1蛋白可用来鉴别和分离干细胞
生物谷：美国研究人员发现，一种特定蛋白也许可用来区分干细胞和干细胞分化的细胞，从而使从各种组织中分离干细胞变得简单。
干细胞能分化成其他细胞，但并非一蹴而就，而是分多个阶段完成并在这个过程中逐渐失去干细胞的特性。干细胞第一阶段分化的是祖细胞。美国约翰斯·霍普金斯大学的尼古拉斯·加亚诺等人发现，一种名为ＣＢＦ１的蛋白与这一阶段密切相关。
研究人员在最新一期《自然》杂志上撰文说，他们用基因工程技术培育出了一种小鼠胚胎，当ＣＢＦ１蛋白发挥作用时，这种胚胎就会发绿光。
他们发现，随着胚胎的发育，其中一些通常被认为是神经干细胞的细胞不再发光，这表明ＣＢＦ１蛋白已失去了效用。进一步研究显示，这些细胞已不再是真正的神经干细胞，而是分化成了祖细胞。研究人员因此推测，ＣＢＦ１蛋白能区分神经干细胞是否已发育成祖细胞。
实验还证明，当神经干细胞中的ＣＢＦ１蛋白被“关闭”时，神经干细胞迅速分化为祖细胞。不过，当ＣＢＦ１蛋白被再次“打开”时，祖细胞并不能再还原为干细胞。研究人员说，从生物化学角度看，一旦ＣＢＦ１蛋白被“关闭”，“所发生的一切就好似开通了一条单行道”。
研究人员此前进行的另一项小鼠实验表明，在血液干细胞分化过程中，ＣＢＦ１蛋白也扮演着同样角色。他们因此推测，ＣＢＦ１蛋白能在多个组织中用来区分干细胞和干细胞分化的细胞。
原始出处:
Nature advance online publication 26 August 2007 | doi:10.1038/nature06090; Received 28 May 2007; Accepted 12 July 2007; Published online 26 August 2007
Differential Notch signalling distinguishes neural stem cells from intermediate progenitors
Ken-ichi Mizutani1,2,5, Keejung Yoon1,2,5,6, Louis Dang1,3, Akinori Tokunaga1,2 & Nicholas Gaiano1,2,3,4
- Institute for Cell Engineering,
- Department of Neurology,
- Department of Neuroscience, and,
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
- These authors contributed equally to this work.
- Present address: Division of Brain Diseases, Center for Biomedical Sciences, National Institute of Health, Tongil-Lo 194, Eunpyung-Gu, Seoul, 122-701, Korea.
Correspondence to: Nicholas Gaiano1,2,3,4 Correspondence and requests for materials should be addressed to N.G. (Email: gaiano@jhmi.edu).
During brain development, neurons and glia are generated from a germinal zone containing both neural stem cells (NSCs) and more limited intermediate neural progenitors (INPs)1, 2, 3. The signalling events that distinguish between these two proliferative neural cell types remain poorly understood. The Notch signalling pathway is known to maintain NSC character and to inhibit neurogenesis, although little is known about the role of Notch signalling in INPs. Here we show that both NSCs and INPs respond to Notch receptor activation, but that NSCs signal through the canonical Notch effector C-promoter binding factor 1 (CBF1), whereas INPs have attenuated CBF1 signalling. Furthermore, whereas knockdown of CBF1 promotes the conversion of NSCs to INPs, activation of CBF1 is insufficient to convert INPs back to NSCs. Using both transgenic and transient in vivo reporter assays we show that NSCs and INPs coexist in the telencephalic ventricular zone and that they can be prospectively separated on the basis of CBF1 activity. Furthermore, using in vivo transplantation we show that whereas NSCs generate neurons, astrocytes and oligodendrocytes at similar frequencies, INPs are predominantly neurogenic. Together with previous work on haematopoietic stem cells4, this study suggests that the use or blockade of the CBF1 cascade downstream of Notch is a general feature distinguishing stem cells from more limited progenitors in a variety of tissues.
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