2012年9月3日 訊 /生物谷BIOON/ --神經(jīng)干細(xì)胞是一種成體干細(xì)胞,，能夠分化為神經(jīng)元,、星形膠質(zhì)細(xì)胞,、少突膠質(zhì)細(xì)胞，并且能夠自我更新從而足以提供大量組成腦組織的細(xì)胞,。神經(jīng)干細(xì)胞的標(biāo)記物包括巢蛋白(nestin),、多唾液酸神經(jīng)細(xì)胞粘附分子(polysiolylated neural cell adhesion molecule, PSA-NCAM)、p75神經(jīng)營養(yǎng)因子受體 和Musashi1等,。長期以來，科學(xué)家們認(rèn)為成年哺乳動(dòng)物神經(jīng)元是不能再生的,，遇到損傷后只能由神經(jīng)膠質(zhì)細(xì)胞來替換,，而不能通過產(chǎn)生新的神經(jīng)元來加以修復(fù)。不過近年來的一些研究表明,，成年哺乳動(dòng)物的腦中存在神經(jīng)干細(xì)胞 ,，而且這些干細(xì)胞具有分化為神經(jīng)元和神經(jīng)膠質(zhì)細(xì)胞的潛能。然而,，調(diào)控哺乳動(dòng)物成體干細(xì)胞字我們更新和分化的細(xì)胞機(jī)制在很大程度上仍是個(gè)迷,。
在這項(xiàng)新研究中，來自加拿大多倫多病童醫(yī)院,、多倫多大學(xué)和奧地利維也納醫(yī)科大學(xué)的研究人員證實(shí)RNA結(jié)合蛋白Staufen2(Stau2)不對稱地定位在胚皮層(embryonic cortex)內(nèi)放射狀神經(jīng)膠質(zhì)前體細(xì)胞(radial glial precursor)的端部,，在那里，它與其他的包括Pumilio2(Pum2)和DDX1在內(nèi)的RNA顆粒蛋白和編碼β-肌動(dòng)蛋白和哺乳動(dòng)物蛋白prospero(prox1)的mRNA形成一個(gè)RNA復(fù)合物,。通過功能性抑制Stau2,、Pum2或DDX1表達(dá)來破壞這種復(fù)合物能夠?qū)е路派錉钌窠?jīng)膠質(zhì)前體細(xì)胞提前分化為神經(jīng)元以及 prox1 mRNA錯(cuò)誤定位和錯(cuò)誤表達(dá)。這就證實(shí)依賴Stau2和Pum2的RNA復(fù)合物在哺乳動(dòng)物神經(jīng)干細(xì)胞中直接調(diào)節(jié)諸如prox1 mRNA之類的靶mRNA定位,，而且還可能直接調(diào)節(jié)它們的表達(dá),，這樣就能夠調(diào)節(jié)成體干細(xì)胞維持和分化之間的平衡。
這些發(fā)現(xiàn)人們更加深刻地認(rèn)識哺乳動(dòng)物神經(jīng)干細(xì)胞的維持自我更新和進(jìn)行分化的機(jī)制,，從而為未來開發(fā)出潛在的療法來治療神經(jīng)退化性方面的疾病打下基礎(chǔ),。相關(guān)研究結(jié)果刊登在Cell Stem Cell期刊上。
doi: 10.1016/j.stem.2012.06.010
PMC:
PMID:
An Asymmetrically Localized Staufen2-Dependent RNA Complex Regulates Maintenance of Mammalian Neural Stem Cells
John P. Vessey, Gianluca Amadei, Sarah E. Burns, Michael A. Kiebler, David R. Kaplan, Freda D. Miller
The cellular mechanisms that regulate self-renewal versus differentiation of mammalian somatic tissue stem cells are still largely unknown. Here, we asked whether an RNA complex regulates this process in mammalian neural stem cells. We show that the RNA-binding protein Staufen2 (Stau2) is apically localized in radial glial precursors of the embryonic cortex, where it forms a complex with other RNA granule proteins including Pumilio2 (Pum2) and DDX1, and the mRNAs for β-actin and mammalian prospero, prox1. Perturbation of this complex by functional knockdown of Stau2, Pum2, or DDX1 causes premature differentiation of radial glial precursors into neurons and mislocalization and misexpression of prox1 mRNA. Thus, a Stau2- and Pum2-dependent RNA complex directly regulates localization and, potentially, expression of target mRNAs like prox1 in mammalian neural stem cells, and in so doing regulates the balance of stem cell maintenance versus differentiation
