scholarly journals Timing of gene expression in a cell-fate decision system

2017 ◽  
Author(s):  
Delphine Aymoz ◽  
Carme Solé ◽  
Jean-Jerrold Pierre ◽  
Marta Schmitt ◽  
Eulàlia de Nadal ◽  
...  

AbstractDuring development, morphogens provide extracellular cues allowing cells to select a specific fate by inducing complex transcriptional programs. The mating pathway in budding yeast offers simplified settings to understand this process. Pheromone secreted by the mating partner triggers the activity of a MAPK pathway, which results in the expression of hundreds of genes. Using a dynamic expression reporter, we quantified the kinetics of gene expression in single cells upon exogenous pheromone stimulation and in the physiological context of mating. In both conditions, we observed striking differences in the timing of induction of mating-responsive promoters. Biochemical analyses and generation of synthetic promoter variants demonstrated how the interplay between transcription factor binding and nucleosomes contribute to determine the kinetics of transcription in a simplified cell-fate decision system.One Sentence SummaryQuantitative and dynamic single cell measurements in the yeast mating pathway uncover a complex temporal orchestration of gene expression events.

2018 ◽  
Vol 14 (4) ◽  
Author(s):  
Delphine Aymoz ◽  
Carme Solé ◽  
Jean‐Jerrold Pierre ◽  
Marta Schmitt ◽  
Eulàlia de Nadal ◽  
...  

2017 ◽  
Author(s):  
Britta Werthmann ◽  
Wolfgang Marwan

AbstractThe developmental switch to sporulation inPhysarum polycephalumis a phytochrome-mediated far-red light-induced cell fate decision that synchronously encompasses the entire multinucleate plasmodial cell and is associated with extensive reprogramming of the transcriptome. By repeatedly taking samples of single cells after delivery of a light stimulus pulse, we analysed differential gene expression in two mutant strains and in a heterokaryon of the two strains all of which display a different propensity for making the cell fate decision. Multidimensional scaling of the gene expression data revealed individually different single cell trajectories eventually leading to sporulation. Characterization of the trajectories as walks through states of gene expression discretized by hierarchical clustering allowed the reconstruction of Petri nets that model and predict the observed behavior. Structural analyses of the Petri nets indicated stimulus- and genotype-dependence of both, single cell trajectories and of the quasipotential landscape through which these trajectories are taken. The Petri net-based approach to the analysis and decomposition of complex cellular responses and of complex mutant phenotypes may provide a scaffold for the data-driven reconstruction of causal molecular mechanisms that shape the topology of the quasipotential landscape.


Nature ◽  
2006 ◽  
Vol 439 (7075) ◽  
pp. 502-502
Author(s):  
Alejandro Colman-Lerner ◽  
Andrew Gordon ◽  
Eduard Serra ◽  
Tina Chin ◽  
Orna Resnekov ◽  
...  

Nature ◽  
2005 ◽  
Vol 437 (7059) ◽  
pp. 699-706 ◽  
Author(s):  
Alejandro Colman-Lerner ◽  
Andrew Gordon ◽  
Eduard Serra ◽  
Tina Chin ◽  
Orna Resnekov ◽  
...  

2021 ◽  
Author(s):  
Megan K. Franke ◽  
Adam L. MacLean

The role of cell-cell communication in cell fate decision-making has not been well-characterized through a dynamical systems perspective. To do so, here we develop multiscale models that couple cell-cell communication with cell-internal gene regulatory network dynamics. This allows us to study the influence of external signaling on cell fate decision-making at the resolution of single cells. We study the granulocyte-monocyte vs. megakaryocyte-erythrocyte fate decision, dictated by the GATA1-PU.1 network, as an exemplary bistable cell fate system, modeling the cell-internal dynamic with ordinary differential equations and the cell-cell communication via a Poisson process. We show that, for a wide range of cell communication topologies, subtle changes in signaling can lead to dramatic changes in cell fate. We find that cell-cell coupling can explain how populations of heterogeneous cell types can arise. Analysis of intrinsic and extrinsic cell-cell communication noise demonstrates that noise alone can alter the cell fate decision-making boundaries. These results illustrate how external signals alter transcriptional dynamics, and provide insight into hematopoietic cell fate decision-making.


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