Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
J Mol Neurosci. 2010 Sep;42(1):35-43. doi: 10.1007/s12031-010-9362-9. Epub 2010 May 1.
Although stem cells can proliferate and differentiate through the completion of cell cycle progression, little is known about the genes and molecular mechanisms controlling this process. Here, we investigated the effect of the inhibition of cell cycle by cyclin D1 gene knockout on proliferation and differentiation of neural stem cells (NSCs). Knockout of cyclin D1 induced the cultured neural stem cells arrested at the G0/G1 phase as detected by flow cytometry. Cyclin D1 knockout led to the apoptosis of NSCs and inhibited the differentiation into astrocytes without affecting the differentiation into neurons. We further demonstrated that a significant reduction of BrdU+ cells in the subgranular zone of the dentate gyrus and subventricular zone was found in cyclin D1 gene knockout (cyclin D1(-/-)) mice compared with cyclin D1(+/+) and cyclin D1(+/-) mice. These observations demonstrated that cyclin D1 plays essential roles in the proliferation and differentiation of neural stem cells.
虽然干细胞可以通过完成细胞周期进展来增殖和分化，但对于控制这一过程的基因和分子机制知之甚少。在这里，我们研究了细胞周期抑制对神经干细胞（NSC）增殖和分化的影响。通过流式细胞术检测到，cyclin D1 基因敲除会诱导培养的神经干细胞停滞在 G0/G1 期。cyclin D1 敲除导致 NSCs 凋亡，并抑制向星形胶质细胞分化，而不影响向神经元分化。我们进一步证明，与 cyclin D1(+/+)和 cyclin D1(+/-)小鼠相比，cyclin D1 基因敲除（cyclin D1(-/-)）小鼠齿状回颗粒下层区和脑室下区的 BrdU+细胞明显减少。这些观察结果表明，cyclin D1 在神经干细胞的增殖和分化中发挥着重要作用。
