在生物個(gè)體的發(fā)育中,,成體干細(xì)胞起著不可忽視的作用,,它能夠維持組織結(jié)構(gòu)穩(wěn)定,,并修復(fù)受損的組織,。然而隨著年齡的增長,成體干細(xì)胞會發(fā)生一些細(xì)微的變化,,這使得有機(jī)體維持自身內(nèi)環(huán)境穩(wěn)定的能力變差,,導(dǎo)致組織的自我修復(fù)和再生能力大不如從前。
在果蠅的睪丸組織中,,隨著年齡的增長,,一種名為Unpaired(Upd)的因子表達(dá)量會減少,而Upd在維持生殖干細(xì)胞自我更新中起重要作用,。Upd的減少導(dǎo)致雄性生殖干細(xì)胞自我更新能力下降,,生殖干細(xì)胞的數(shù)量也就減少了。
本文的研究人員發(fā)現(xiàn),,IGF-II信使RNA結(jié)合蛋白(IGF-II messenger RNA binding protein,,lmp)能夠中和內(nèi)源性小RNA對updRNA的降解作用,從而使updRNA更穩(wěn)定,。在老年的雄性果蠅中,,跟udp一樣,lmp的表達(dá)量也減少了,。當(dāng)microRNAlet-7靶向lmp導(dǎo)致其的表達(dá)量減少后,,udp的mRNA由于失去了保護(hù),更加容易被降解,。了解干細(xì)胞老化機(jī)制和年齡給干細(xì)胞帶來的影響有利于更好的研究如何在老年個(gè)體中進(jìn)行干細(xì)胞治療,。(生物谷 Bioon.com )
doi:10.1038/nature11061
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The let-7–Imp axis regulates ageing of the Drosophila testis stem-cell niche
Hila Toledano, Cecilia D’Alterio, Benjamin Czech, Erel Levine & D. Leanne Jones
Adult stem cells support tissue homeostasis and repair throughout the life of an individual. During ageing, numerous intrinsic and extrinsic changes occur that result in altered stem-cell behaviour and reduced tissue maintenance and regeneration. In the Drosophila testis, ageing results in a marked decrease in the self-renewal factor Unpaired (Upd), leading to a concomitant loss of germline stem cells. Here we demonstrate that IGF-II messenger RNA binding protein (Imp) counteracts endogenous small interfering RNAs to stabilize upd (also known as os) RNA. However, similar to upd, Imp expression decreases in the hub cells of older males, which is due to the targeting of Imp by the heterochronic microRNA let-7. In the absence of Imp, upd mRNA therefore becomes unprotected and susceptible to degradation. Understanding the mechanistic basis for ageing-related changes in stem-cell behaviour will lead to the development of strategies to treat age-onset diseases and facilitate stem-cell-based therapies in older individuals.