Heritable stochastic switching revealed by single-cell genealogy.
Heritable stochastic switching revealed by single-cell genealogy.
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DOI：
10.1371/journal.pbio.0050239
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发表时间：
2007-09
期刊：
影响因子：
9.8
通讯作者：
van Oudenaarden A
中科院分区：
文献类型：
--
作者：
Kaufmann BB;Yang Q;Mettetal JT;van Oudenaarden A
细胞因子如蛋白质和RNA的分配和随后的遗传是细胞分裂的普遍特征。然而，这种非遗传性遗传如何影响随后的基因表达变化的直接定量测量一直缺乏。我们跟踪了酿酒酵母的家族，因为它们在两个半稳定的表观遗传状态之间切换。我们发现，在两个细胞分裂很久之后，它们继续以同步的方式切换，而单个细胞的切换时间呈指数分布。通过将这些结果与泊松过程进行比较，我们发现表观遗传状态的时间演化最初取决于遗传因素，随机过程需要几代人来解相关密切相关的细胞。最后，一个简单的随机模型表明，一个单一的波动的调节蛋白，在大爆发合成可以解释我们的大部分结果。当细胞分裂时，不仅DNA，而且整个基因表达模式都可以从母体细胞传递到子细胞。一旦细胞分裂完成，随机过程会导致这种模式发生变化，随着时间的推移，密切相关的细胞越来越不相似。我们测量了单个酵母细胞中动态基因表达状态的遗传。我们使用了一个工程网络，其中单个细胞在两个半稳定状态（ON和OFF）之间切换，即使在恒定的环境中。在细胞物理分离几代之后，许多对密切相关的细胞几乎同步切换。我们通过测量母细胞在子细胞已经发生转换的情况下发生转换的可能性来量化这种影响。这产生了一个条件概率分布，这是非常不同的指数在整个人口的开关细胞。我们测量开关细胞之间的这种相关性持续的程度，通过比较我们的结果与模型泊松过程。总之，这些发现证明了动态基因表达状态的遗传，其分裂后的变化包括由噪声引起的随机因素以及源于两个相关细胞共享历史的相关因素。最后，我们构建了一个模型，证明我们的主要发现可以用单个调节蛋白水平的爆发式波动来解释。当细胞分裂时，每个子细胞继承母亲细胞的一部分内容物。如果内容包括一个具有反馈回路的调节系统，姐妹细胞会同步切换状态。
The partitioning and subsequent inheritance of cellular factors like proteins and RNAs is a ubiquitous feature of cell division. However, direct quantitative measures of how such nongenetic inheritance affects subsequent changes in gene expression have been lacking. We tracked families of the yeast Saccharomyces cerevisiae as they switch between two semi-stable epigenetic states. We found that long after two cells have divided, they continued to switch in a synchronized manner, whereas individual cells have exponentially distributed switching times. By comparing these results to a Poisson process, we show that the time evolution of an epigenetic state depends initially on inherited factors, with stochastic processes requiring several generations to decorrelate closely related cells. Finally, a simple stochastic model demonstrates that a single fluctuating regulatory protein that is synthesized in large bursts can explain the bulk of our results. When cells divide, not only DNA but an entire pattern of gene expression can be passed from mother to daughter cell. Once cell division is complete, random processes cause this pattern to change, with closely related cells growing less similar over time. We measured inheritance of a dynamic gene-expression state in single yeast cells. We used an engineered network where individual cells switch between two semi-stable states (ON and OFF), even in a constant environment. Several generations after cells have physically separated, many pairs of closely related cells switch in near synchrony. We quantified this effect by measuring how likely a mother cell is to have switched given that the daughter cell has already switched. This yields a conditional probability distribution that is very different from the exponential one found in the entire population of switching cells. We measured the extent to which this correlation between switching cells persists by comparing our results with a model Poisson process. Together, these findings demonstrate the inheritance of a dynamic gene expression state whose post-division changes include both random factors arising from noise as well as correlated factors that originate in two related cells' shared history. Finally, we constructed a model that demonstrates that our major findings can be explained by burst-like fluctuations in the levels of a single regulatory protein. When cells divide, each daughter cell inherits a share of the contents of the mother. If the contents include a regulatory system with a feedback loop, sister cells switch states in synchrony.
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影响因子：
9.8
作者：
Brickner DG;Cajigas I;Fondufe-Mittendorf Y;Ahmed S;Lee PC;Widom J;Brickner JH
通讯作者：
Brickner JH
影响因子：
30.8
作者：
Becskei, A;Kaufmann, BB;van Oudenaarden, A
通讯作者：
van Oudenaarden, A
DOI：
10.1073/pnas.43.7.553
发表时间：
1957-01-01
影响因子：
11.1
作者：
NOVICK, A;WEINER, M
通讯作者：
WEINER, M
影响因子：
16
作者：
Blake, William J.;Balazsi, Gbor;Collins, James J.
通讯作者：
Collins, James J.
影响因子：
56.9
作者：
Patino, MM;Liu, JJ;Lindquist, S
通讯作者：
Lindquist, S