哈佛医学院细胞分化研究中心，麻省理工学院计算机系统生物学系的研究者Peter K.Sorger等人在12日的Nature在线版上发表肿瘤研究的最新进展，文章标题为：Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis。
在生物体内不同的细胞具有不同的细胞表达模式，这一差异造就了千差万别的细胞类型，造就了生物多样性。对哺乳动物细胞而言，每个细胞的蛋白表达水平都存在差异，这一差异使得不同的细胞对相同的生理刺激都产生各具特点的生物反应。
在TRAIL（肿瘤坏死因子相关的细胞凋亡诱导配基）介导的细胞凋亡程序中，就算来自同一个克隆系的细胞对细胞凋亡程序都产生截然不同的反应，有些细胞经诱导后进入凋亡程序，有些细胞则不然，不同的细胞面对相同的程序会有不同的命运，就好像来自同卵的双胞胎虽然样貌一样但性格迥然。即便是对细胞凋亡程序有效的细胞，它们接受TRAIL诱导的作用和Caspase的作用也各有各的不同。这就是研究人员发现的在自然情况下不同的蛋白水平导致每个细胞对细胞凋亡程度的应答差异。文章第一作者Sabrina L. Spencer称，相同的细胞会有不同的命运。Sabrina L. Spencer是Peter K.Sorger实验室的研究生。也许大哲学家莱布尼茨所说的世界上没有两片相同的叶子这一理念也同样适合于细胞个体。
为什么会有这种情况发生呢？研究者们解开了谜团，他们发现来自一个克隆细胞系的子代细胞其蛋白表达情况在最初与亲代是一致的，这种一致性只保持一个短暂的时间，可以说是昙花一现。之后，蛋白合成过程会迅速地改变每个细胞的蛋白水平，形成蛋白水平各异的细胞。
正是由于存在这一类的差异，癌细胞对化疗药物可能产生千差万别的反应，有些癌细胞在化疗药物的作用下发生凋亡而死，而有些癌细胞却对化学药物不敏感，这一结果导致化疗药物对癌细胞的作用不均一。
这一研究成果改变了人们以往对细胞的传统认识，每个细胞都不同，也许这为癌症的治疗开辟了新的道路。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
