哈佛醫(yī)學(xué)院細(xì)胞分化研究中心,，麻省理工學(xué)院計算機系統(tǒng)生物學(xué)系的研究者Peter K.Sorger等人在12日的Nature在線版上發(fā)表腫瘤研究的最新進(jìn)展，文章標(biāo)題為：Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis,。
在生物體內(nèi)不同的細(xì)胞具有不同的細(xì)胞表達(dá)模式,，這一差異造就了千差萬別的細(xì)胞類型，造就了生物多樣性,。對哺乳動物細(xì)胞而言,，每個細(xì)胞的蛋白表達(dá)水平都存在差異，這一差異使得不同的細(xì)胞對相同的生理刺激都產(chǎn)生各具特點的生物反應(yīng),。
在TRAIL（腫瘤壞死因子相關(guān)的細(xì)胞凋亡誘導(dǎo)配基）介導(dǎo)的細(xì)胞凋亡程序中,，就算來自同一個克隆系的細(xì)胞對細(xì)胞凋亡程序都產(chǎn)生截然不同的反應(yīng)，有些細(xì)胞經(jīng)誘導(dǎo)后進(jìn)入凋亡程序,，有些細(xì)胞則不然,，不同的細(xì)胞面對相同的程序會有不同的命運，就好像來自同卵的雙胞胎雖然樣貌一樣但性格迥然,。即便是對細(xì)胞凋亡程序有效的細(xì)胞,，它們接受TRAIL誘導(dǎo)的作用和Caspase的作用也各有各的不同,。這就是研究人員發(fā)現(xiàn)的在自然情況下不同的蛋白水平導(dǎo)致每個細(xì)胞對細(xì)胞凋亡程度的應(yīng)答差異。文章第一作者Sabrina L. Spencer稱,，相同的細(xì)胞會有不同的命運,。Sabrina L. Spencer是Peter K.Sorger實驗室的研究生。也許大哲學(xué)家萊布尼茨所說的世界上沒有兩片相同的葉子這一理念也同樣適合于細(xì)胞個體,。
為什么會有這種情況發(fā)生呢,？研究者們解開了謎團(tuán)，他們發(fā)現(xiàn)來自一個克隆細(xì)胞系的子代細(xì)胞其蛋白表達(dá)情況在最初與親代是一致的,，這種一致性只保持一個短暫的時間，可以說是曇花一現(xiàn),。之后,，蛋白合成過程會迅速地改變每個細(xì)胞的蛋白水平，形成蛋白水平各異的細(xì)胞,。
正是由于存在這一類的差異,，癌細(xì)胞對化療藥物可能產(chǎn)生千差萬別的反應(yīng)，有些癌細(xì)胞在化療藥物的作用下發(fā)生凋亡而死,，而有些癌細(xì)胞卻對化學(xué)藥物不敏感,，這一結(jié)果導(dǎo)致化療藥物對癌細(xì)胞的作用不均一。
這一研究成果改變了人們以往對細(xì)胞的傳統(tǒng)認(rèn)識,，每個細(xì)胞都不同,，也許這為癌癥的治療開辟了新的道路。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature advance online publication 12 April 2009 | doi:10.1038/nature08012
Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis
Sabrina L. Spencer1,2,3, Suzanne Gaudet1,4,3, John G. Albeck1, John M. Burke1 & Peter K. Sorger1
1 Center for Cell Decision Processes, Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
2 Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
3 These authors contributed equally to this work.
4 Present address: Department of Cancer Biology, Dana-Farber Cancer Institute, and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
In microorganisms, noise in gene expression gives rise to cell-to-cell variability in protein concentrations1, 2, 3, 4, 5, 6, 7. In mammalian cells, protein levels also vary8, 9, 10 and individual cells differ widely in their responsiveness to uniform physiological stimuli11, 12, 13, 14, 15. In the case of apoptosis mediated by TRAIL (tumour necrosis factor (TNF)-related apoptosis-inducing ligand) it is common for some cells in a clonal population to die while others survive—a striking divergence in cell fate. Among cells that die, the time between TRAIL exposure and caspase activation is highly variable. Here we image sister cells expressing reporters of caspase activation and mitochondrial outer membrane permeabilization after exposure to TRAIL. We show that naturally occurring differences in the levels or states of proteins regulating receptor-mediated apoptosis are the primary causes of cell-to-cell variability in the timing and probability of death in human cell lines. Protein state is transmitted from mother to daughter, giving rise to transient heritability in fate, but protein synthesis promotes rapid divergence so that sister cells soon become no more similar to each other than pairs of cells chosen at random. Our results have implications for understanding 'fractional killing' of tumour cells after exposure to chemotherapy, and for variability in mammalian signal transduction in general.
