Dissecting genealogy and cell cycle as sources of cell-to-cell variability in MAPK signaling using high-throughput lineage tracking
Dissecting genealogy and cell cycle as sources of cell-to-cell variability in MAPK signaling using high-throughput lineage tracking
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使用高通量谱系追踪剖析谱系和细胞周期作为 MAPK 信号传导中细胞间变异的来源
DOI：
10.1073/pnas.1215850110
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
C. Hansen
中科院分区：
文献类型：
--
作者：
Markéta Řičicová;M. Hamidi;Adam Quiring;A. Niemistö;E. Emberly;C. Hansen
细胞，即使是具有相同基因型的细胞，对外界刺激的反应也表现出差异。这种可变性源于细胞成分的丰度、定位和状态的差异。这种非遗传差异可能在连续几代之间遗传，也可能受到细胞周期、年龄或不同途径之间相互作用等过程的影响。为了解决非遗传遗传性和细胞周期在细胞间变异中的贡献，我们开发了一个高通量和全自动微流控平台，允许在大量临时变化的培养基条件下和使用多种菌株同时测量基因表达，细胞周期，年龄和谱系信息。我们应用这项技术来研究非基因遗传在酵母信息素信号细胞异质性中的作用。我们的数据表明，对信息素的反应能力是代代相传的，相关细胞之间的反应相关性强度受到信号通路扰动的影响。我们观察到ste50Δ突变株对信息素的高度异质反应源于母亲和女儿之间独特的不对称反应。另一方面，研究发现fus3Δ细胞在母细胞和子细胞之间表现出异常高的相关性，这是由于fus3Δ母细胞的细胞周期周期延长和信息素途径的细胞周期调节减少的结合。我们的研究结果有助于理解细胞异质性的起源，并证明了在几个参数上生成单细胞数据的自动化平台的重要性。
Cells, even those having identical genotype, exhibit variability in their response to external stimuli. This variability arises from differences in the abundance, localization, and state of cellular components. Such nongenetic differences are likely heritable between successive generations and can also be influenced by processes such as cell cycle, age, or interplay between different pathways. To address the contribution of nongenetic heritability and cell cycle in cell-to-cell variability we developed a high-throughput and fully automated microfluidic platform that allows for concurrent measurement of gene expression, cell-cycle periods, age, and lineage information under a large number of temporally changing medium conditions and using multiple strains. We apply this technology to examine the role of nongenetic inheritance in cell heterogeneity of yeast pheromone signaling. Our data demonstrate that the capacity to respond to pheromone is passed across generations and that the strength of the response correlations between related cells is affected by perturbations in the signaling pathway. We observe that a ste50Δ mutant strain exhibits highly heterogeneous response to pheromone originating from a unique asymmetry between mother and daughter response. On the other hand, fus3Δ cells were found to exhibit an unusually high correlation between mother and daughter cells that arose from a combination of extended cell-cycle periods of fus3Δ mothers, and decreased cell-cycle modulation of the pheromone pathway. Our results contribute to the understanding of the origins of cell heterogeneity and demonstrate the importance of automated platforms that generate single-cell data on several parameters.
DOI：
10.1073/pnas.88.21.9392
发表时间：
1991-11-01
影响因子：
11.1
作者：
ELION, EA;BRILL, JA;FINK, GR
通讯作者：
FINK, GR
影响因子：
6.1
作者：
Falconnet D;Niemistö A;Taylor RJ;Ricicova M;Galitski T;Shmulevich I;Hansen CL
通讯作者：
Hansen CL
影响因子：
64.8
作者：
Eilken, Hanna M.;Nishikawa, Shin-Ichi;Schroeder, Timm
通讯作者：
Schroeder, Timm