关于大多数干细胞体系中存在不同增殖细胞类型的观点是被广泛接受的，但人们对这些干细胞与受限制的“先祖亚集”（progenitor  subsets）细胞之间的差别却并不是很了解。现在，在约翰·霍普金斯大学从事研究工作的一个小组发现了正在发育中的小鼠脑中两个不同细胞类群（它们是“真正的”神经干细胞，是相似的、但功能稍差的先祖细胞）之间是怎样区分的。干细胞分步成熟，逐渐脱去“干细胞”属性。第一步是通过决定Notch（一种在很多组织中调控干细胞的蛋白）下游的信号如何传输来将干细胞变成“先祖细胞”。然后，两个细胞类型分化，这里的关键因素是一种Notch信号作用蛋白（被称为CBF1）是否是具有活性的。CBF1信号通道在血液干细胞中起相同作用，所以它可能是一个将干细胞同先祖细胞区分开来的通用“开关”。

原始出处：

Nature449, 351-355 (20 September 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

1.                      Institute for Cell Engineering,

2.                      Department of Neurology,

3.                      Department of Neuroscience, and,

4.                      Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA

5.                      These authors contributed equally to this work.

6.                      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.

                                                 摘自《生物谷》