日本研究人員在新一期美國《神經(jīng)元》雜志上報告說,他們經(jīng)動物實驗確認,,神經(jīng)干細胞內(nèi)的蛋白質(zhì)“Hes1”會在神經(jīng)干細胞分化成神經(jīng)細胞時發(fā)生有節(jié)律的增減,,控制這種干細胞分化的時機。
日本京都大學(xué)教授影山龍一郎的研究小組,,通過分析實驗鼠胎兒腦內(nèi)所含的神經(jīng)干細胞,,發(fā)現(xiàn)其中的“Hes1”蛋白質(zhì)以2小時至3小時為周期反復(fù)增減,神經(jīng)干細胞也隨著這種增減不斷自我復(fù)制,,向神經(jīng)細胞轉(zhuǎn)化,。而如果使“Hes1”含量下降并使其幾乎不發(fā)揮作用,那么神經(jīng)干細胞就不能分化成神經(jīng)細胞,。
人們期待通過移植神經(jīng)干細胞在神經(jīng)疾病領(lǐng)域進行再生治療,,然而神經(jīng)干細胞在動物體外幾乎不增殖,這是目前將這種干細胞用于再生治療尚待解決的課題,。
研究人員表示,,以這項成果為基礎(chǔ),,找到控制神經(jīng)干細胞分化節(jié)律的方法,就有望在人體外控制用于治療的神經(jīng)干細胞的增殖和分化,,進而更有效地移植,。
生物谷推薦原始出處:
Neuron, Vol 58, 52-64, 10 April 2008
Oscillations in Notch Signaling Regulate Maintenance of Neural Progenitors
Hiromi Shimojo,1 Toshiyuki Ohtsuka,1 and Ryoichiro Kageyama1,
1 Institute for Virus Research, Kyoto University, and Japan Science and Technology Agency, CREST, Kyoto 606-8507, Japan
Summary
Expression of the Notch effector gene Hes1 is required for maintenance of neural progenitors in the embryonic brain, but persistent and high levels of Hes1 expression inhibit proliferation and differentiation of these cells. Here, by using a real-time imaging method, we found that Hes1 expression dynamically oscillates in neural progenitors. Furthermore, sustained overexpression of Hes1 downregulates expression of proneural genes, Notch ligands, and cell cycle regulators, suggesting that their proper expression depends on Hes1 oscillation. Surprisingly, the proneural gene Neurogenin2 (Ngn2) and the Notch ligand Delta-like1 (Dll1) are also expressed in an oscillatory manner by neural progenitors, and inhibition of Notch signaling, a condition known to induce neuronal differentiation, leads to downregulation of Hes1 and sustained upregulation of Ngn2 and Dll1. These results suggest that Hes1 oscillation regulates Ngn2 and Dll1 oscillations, which in turn lead to maintenance of neural progenitors by mutual activation of Notch signaling.