人類機(jī)體擁有強(qiáng)大的愈合能力,，但治療腦部疾病卻并非易事，神經(jīng)元作為重要的大腦細(xì)胞,，其再生能力往往有限,，盡管如此,，干細(xì)胞卻是一種天然的支持形式，是我們胚胎發(fā)育中所留下的重要遺跡,。隨著年齡增長(zhǎng),，神經(jīng)干細(xì)胞就會(huì)休眠，當(dāng)機(jī)體需要修復(fù)時(shí)其很難再次蘇醒,，盡管能通過利用神經(jīng)干細(xì)胞來治療機(jī)體神經(jīng)性障礙,，但直到最近科學(xué)家們才找到了神經(jīng)干細(xì)胞“沉睡”的機(jī)制。

近日,，一項(xiàng)刊登在國(guó)際雜志Genes & Development上的研究報(bào)告中,，來自日本京都大學(xué)的科學(xué)家們通過對(duì)小鼠的大腦化學(xué)機(jī)制進(jìn)行研究發(fā)現(xiàn),，基因表達(dá)的起起伏伏或會(huì)讓神經(jīng)干細(xì)胞從睡夢(mèng)中醒來,，相關(guān)研究結(jié)果有望幫助科學(xué)家們理解大腦再生的潛力,，并開發(fā)治療多種神經(jīng)性疾病的新型療法,。深入研究后,，研究人員重點(diǎn)關(guān)注了一種在成體細(xì)胞中強(qiáng)烈表達(dá)的名為Hes1的蛋白質(zhì),，正常情況下,，其會(huì)抑制名為Ascl1蛋白質(zhì)的產(chǎn)生,，其中一小部分是由活性干細(xì)胞周期性產(chǎn)生的,。隨著時(shí)間延續(xù),，研究人員監(jiān)測(cè)這兩種蛋白質(zhì)的產(chǎn)生，發(fā)現(xiàn)了一種波形模式,，其能促進(jìn)干細(xì)胞蘇醒并轉(zhuǎn)化成為大腦中的神經(jīng)元細(xì)胞,。

當(dāng)研究者敲除了制造Hes1所需要的遺傳代碼后，細(xì)胞就開始制造更多的Ascl1蛋白質(zhì),，隨后激活幾乎所有的神經(jīng)干細(xì)胞,，研究者Kageyama表示，最關(guān)鍵在于相同的基因同時(shí)負(fù)責(zé)這些干細(xì)胞的活性和靜息狀態(tài),。因此,，更好地理解不同表達(dá)動(dòng)態(tài)模式下的調(diào)節(jié)性機(jī)制或能幫助研究者開啟休眠的干細(xì)胞，并利用其來治療一系列神經(jīng)變性疾病,。

推薦閱讀原文：

High Hes1 expression and resultant Ascl1 suppression regulate quiescent vs. active neural stem cells in the adult mouse brain.

Somatic stem/progenitor cells are active in embryonic tissues but quiescent in many adult tissues. The detailed mechanisms that regulate active versus quiescent stem cell states are largely unknown. In active neural stem cells, Hes1 expression oscillates and drives cyclic expression of the proneural gene Ascl1, which activates cell proliferation. Here, we found that in quiescent neural stem cells in the adult mouse brain, Hes1 levels are oscillatory, although the peaks and troughs are higher than those in active neural stem cells, causing Ascl1 expression to be continuously suppressed. Inactivation of Hes1 and its related genes up-regulates Ascl1 expression and increases neurogenesis. This causes rapid depletion of neural stem cells and premature termination of neurogenesis. Conversely, sustained Hes1 expression represses Ascl1, inhibits neurogenesis, and maintains quiescent neural stem cells. In contrast, induction of Ascl1 oscillations activates neural stem cells and increases neurogenesis in the adult mouse brain. Thus, Ascl1 oscillations, which normally depend on Hes1 oscillations, regulate the active state, while high Hes1 expression and resultant Ascl1 suppression promote quiescence in neural stem cells.