【转帖】神经干细胞如何决定增殖及分化

Researchers at Duke-NUS Graduate Medical School in Singapore have uncovered a novel feedback mechanism that controls the delicate balance of brain stem cells.Zif, a newly discovered protein, controls whether brain stem cells renew themselves as stem cells or differentiate into a dedicated type of neuron (nerve cell).
在杜克和新加坡国立大学研究生医学院的研究人员揭示了控制大脑精细平衡一种新的反馈机制，新发现的蛋白质Zif，控制大脑干细胞的自我更新或分化成专用型的神经元（神经细胞）。

In preclinical studies, the researchers showed that Zif is important for inhibiting overgrowth of neural stem cells in fruit flies (genus Drosophila) by ensuring that a proliferation factor (known as aPKC) maintains appropriate levels in neural stem cells.
在临床前的研究中，研究人员发现在果蝇ZIF是抑制神经干细胞增生的重要因素，通过调控增殖因子（已经知道的aPKC）在神经干细胞中维持在适当的水平。

"There is a Zif-related protein in humans, and its function remains to be analyzed," said senior and corresponding author Hongyan Wang, Ph.D. "Our finding has paved the way for future study of this human protein in the context of diseases, including glioblastomas, the most severe form of brain tumors."
“人体中有Zif相关的蛋白，其功能还有待分析”，资深的通讯作者王红岩博士说，“我们的发现为这类疾病，包括胶质母细胞瘤，脑肿瘤等人类蛋白质的后续研究铺平了道路。”

She said it may be "possible to manipulate Zif function into a form of therapy against diseases, including cancer."The study was published in the Nov. 16 issue of Developmental Cell journal.The findings suggest that a lack of Zif protein expression correlates with neural stem cell overpopulation in Drosophila
她说通过调控ZIF功能可能是对疾病可以操纵的治疗，包括癌症在内。这项研究是在11月16日的《Developmental Cell》上发表的。结果表明，一个缺乏相关的ZIF蛋白表达与果蝇神经干细胞过度增殖有关。

The mechanism is circular: Zif is a transcription factor that inhibits the manufacture of aPKC. But Zif can also be tagged with a phosphate by aPKC, which excludes Zif from the cell nucleus, and leads to Zif inactivation, which in turn means an overgrowth of stem cells.
该机制是循环：ZIF是一种转录因子，抑制aPKC制造。但是，也可以通过磷酸化和aPKC联系，其中不包括来自细胞核的ZIF，并导致的ZIF失活，而这又反过来引起干细胞增殖。

"Next, we would like to investigate the mechanisms of neural stem cells' self-renewal in mammals, and we are looking for the right collaborators," Wang said. "We will also continue to use Drosophila as a powerful model system to uncover critical players in neural stem cell self-renewal so that we can understand the network involved in this regulation."
“下一步，我们想在哺乳动物中探讨神经干细胞的自我更新的机制，我们正在寻找合作者”，他说， “我们还将继续利用强大的模型系统，以揭示果蝇神经干细胞的自我更新的关键成员，这样我们可以了解调节的网络。”

Other authors on the paper included four co-lead authors, Kai Chen Chang and Gisela Garcia Alvarez of the Neuroscience and Behavioral Disorder Program at Duke-NUS Graduate Medical School; Gregory Somers of the Department of Genetics, La Trobe Institute for Molecular Science (LIMS), La Trobe University, in Australia; and Rita Sousa-Nunes of the National Institute for Medical Research, Mill Hill, in London. Fabrizio Rossi is from the Cell Division Group, IRB-Barcelona, PCB, in Barcelona, Swee Beng Soon is also with Duke-NUS Neuroscience and Behavioral Disorder Program, and William Chia and Kai Chen Chang are both with the Temasek Life Science Laboratory in Singapore.
论文的其他作者包括四个共同作者，杜克-新加坡国立大学研究医学院神经科学与行为障碍项目的Kai Chen Chang 和 Gisela Garcia Alvarez，遗传学系的Gregory Somers，澳大利亚La Trobe 大学分子科学研究所（LIMS ）的La Trobe，国立卫生医学研究院的Rita Sousa-Nunes，伦敦的Mill Hill，巴塞罗那细胞分裂组的Fabrizio Rossi，Swee Beng Soon也是杜克-新加坡国立大学研究医学院神经科学与行为障碍项目成员，Cayetano Gonzalez 来自巴塞罗那细胞分裂组，William Chia和 Kai Chen Chang 都是新加坡的生命科学实验室成员。

This work is supported by the Duke-NUS Neuroscience & Behavioral Disorders Signature Research Program funded by A*STAR and Ministry of Health, Ministry of Education in Singapore, and the Singapore National Research Foundation, as well as by Temasek Life Sciences funding.
这项工作是受到杜克大学-新加坡国立大学神经科学神经科学与行为障碍项目和新加坡卫生部以及教育部资助，同时也是新加坡国家研究基金会及Temasek生命科学的资助项目。

http://www.sciencedaily.com/releases/2010/11/101115122635.htm