scholarly journals Disentangling a Complex Response in Cell Reprogramming and Probing the Waddington Landscape by Automatic Construction of Petri Nets

2019 ◽  
Author(s):  
Viktoria Rätzel ◽  
Britta Werthmann ◽  
Markus Haas ◽  
Jan Strube ◽  
Wolfgang Marwan
Keyword(s):  
Petri Nets ◽  
Cell Fate ◽  
Single Cells ◽  
Genetic Alterations ◽  
Basins Of Attraction ◽  
Cellular Reprogramming ◽  
Automatic Construction ◽  
Complex Response ◽  
Uncertain Structure ◽  
Fate Decision

We analyzed the developmental switch to sporulation of a multinucleate Physarum polycephalum plasmodial cell, a complex response to phytochrome photoreceptor activation. Automatic construction of Petri nets from trajectories of differential gene expression in single cells revealed alternative, genotype-dependent interconnected developmental routes and identified metastable states, commitment points, and subsequent irreversible steps together with molecular signatures associated with cell fate decision and differentiation. Formation of transition-invariants in mutants that are locked in a proliferative state is remarkable considering the view that oncogenic alterations may cause the formation of cancer attractors. We conclude that the Petri net approach is useful to probe the Waddington landscape of cellular reprogramming, to disentangle developmental routes for the reconstruction of the gene regulatory network, and to understand how genetic alterations or physiological conditions reshape the landscape eventually creating new basins of attraction. Unraveling the complexity of pathogenesis, disease progression, and drug response or the analysis of attractor landscapes in other complex systems of uncertain structure might be additional fields of application.

scholarly journals Developmental switching inPhysarum polycephalum: Petri net analysis of single cell trajectories of gene expression indicates responsiveness and genetic plasticity of the Waddington quasipotential landscape

2017 ◽  
Author(s):  
Britta Werthmann ◽  
Wolfgang Marwan
Keyword(s):  
Gene Expression ◽  
Petri Nets ◽  
Single Cell ◽  
Cell Fate ◽  
Petri Net ◽  
Single Cells ◽  
Cell Fate Decision ◽  
Stimulus Pulse ◽  
Fate Decision ◽  
Cell Trajectories

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.

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 ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Mapk Pathway ◽  
Single Cells ◽  
Cell Fate Decision ◽  
Decision System ◽  
Mating Partner ◽  
Mating Pathway ◽  
Fate Decision ◽  
Kinetics Of

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.

scholarly journals Epigenetic control of cell fate - an interview with Prof. Maria-Elena Torres-Padilla

2020 ◽  
Vol 52 ◽  
Author(s):  
Jesús Chimal-Monroy ◽  
Diana María Escalante-Alcalde
Keyword(s):  
Cell Fate ◽  
Cell Biology ◽  
Cell Lineage ◽  
Cellular Reprogramming ◽  
Cell Fate Decision ◽  
Cell Embryo ◽  
Founding Director ◽  
Fate Decision ◽  
The One ◽  
New Generation

Dr. Maria-Elena Torres-Padilla's research is focused on how cell fate arises from a single-cell embryo, the fertilized egg or zygote. After the initial divisions, cell potency becomes restricted, originating the first cell lineage fates. She studies how epigenetic information controls transitions in cell identity and cellular reprogramming during embryonic development. Currently, she is the founding Director of the Institute of Epigenetics and Stem Cells, Helmholtz Centre, and Professor of Stem Cell Biology at the LMU in Munich. In this interview, Dr. Maria-Elena Torres-Padilla talks to us about her beginnings in the biology field in Mexico. She also tells us about how she became interested in the control of genome regulation within the nucleus during the transition from totipotency to pluripotency and how the control of gene regulation and chromatin organization during the early stages of cell fate decision in the one-cell embryo occurs. She considers that science has no borders; visiting Mexico gives her the possibility to discuss her work with colleagues and the new generation of students trained in Mexico.

scholarly journals A cell atlas of the adult Drosophila midgut

2018 ◽  
Author(s):  
Ruei-Jiun Hung ◽  
Yanhui Hu ◽  
Rory Kirchner ◽  
Fangge Li ◽  
Chiwei Xu ◽  
...  
Keyword(s):  
Cell Fate ◽  
Single Cells ◽  
Enrichment Analysis ◽  
Cell Types ◽  
Gene Set Enrichment Analysis ◽  
Web Based ◽  
Molecular Features ◽  
Gut Hormone ◽  
A Cell ◽  
Fate Decision

AbstractStudies of the adult Drosophila midgut have provided a number of insights on cell type diversity, stem cell regeneration, tissue homeostasis and cell fate decision. Advances in single-cell RNA sequencing (scRNA-seq) provide opportunities to identify new cell types and molecular features. We used inDrop to characterize the transcriptome of midgut epithelial cells and identified 12 distinct clusters representing intestinal stem cells (ISCs), enteroblasts (EBs), enteroendocrine cells (EEs), enterocytes (ECs) from different regions, and cardia. This unbiased approach recovered 90% of the known ISCs/EBs markers, highlighting the high quality of the dataset. Gene set enrichment analysis in conjunction with electron micrographs revealed that ISCs are enriched in free ribosomes and possess mitochondria with fewer cristae. We demonstrate that a subset of EEs in the middle region of the midgut expresses the progenitor marker esg and that individual EEs are capable of expressing up to 4 different gut hormone peptides. We also show that the transcription factor klumpfuss (klu) is expressed in EBs and functions to suppress EE formation. Lastly, we provide a web-based resource for visualization of gene expression in single cells. Altogether, our study provides a comprehensive resource for addressing novel functions of genes in the midgut epithelium.

scholarly journals Disentangling a complex response in cell reprogramming and probing the Waddington landscape by automatic construction of Petri nets

Biosystems ◽  
2020 ◽  
Vol 189 ◽  
pp. 104092 ◽  
Author(s):  
Viktoria Rätzel ◽  
Britta Werthmann ◽  
Markus Haas ◽  
Jan Strube ◽  
Wolfgang Marwan
Keyword(s):  
Petri Nets ◽  
Cell Reprogramming ◽  
Automatic Construction ◽  
Complex Response

scholarly journals A single-cell resolved cell-cell communication model explains lineage commitment in hematopoiesis

2021 ◽  
Author(s):  
Megan K. Franke ◽  
Adam L. MacLean
Keyword(s):  
Decision Making ◽  
Cell Fate ◽  
Single Cells ◽  
System Modeling ◽  
Cell Communication ◽  
Internal Dynamic ◽  
Cell Fate Decision ◽  
Wide Range ◽  
Fate Decision ◽  
Cell Cell

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.

Use of Flexible Materials with a Novel Pressure Driven Equibiaxial Cell Stretching Device for Mechanical Stimulation of Single Mammalian Cells

2003 ◽  
Vol 773 ◽  
Author(s):  
James D. Kubicek ◽  
Stephanie Brelsford ◽  
Philip R. LeDuc
Keyword(s):  
Cell Fate ◽  
Mechanical Stimulation ◽  
Mammalian Cells ◽  
Cellular Response ◽  
Single Cells ◽  
Complex Nature ◽  
Cellular Behavior ◽  
Cell Stretching ◽  
Stimulation Of ◽  
Pressure Driven

AbstractMechanical stimulation of single cells has been shown to affect cellular behavior from the molecular scale to ultimate cell fate including apoptosis and proliferation. In this, the ability to control the spatiotemporal application of force on cells through their extracellular matrix connections is critical to understand the cellular response of mechanotransduction. Here, we develop and utilize a novel pressure-driven equibiaxial cell stretching device (PECS) combined with an elastomeric material to control specifically the mechanical stimulation on single cells. Cells were cultured on silicone membranes coated with molecular matrices and then a uniform pressure was introduced to the opposite surface of the membrane to stretch single cells equibiaxially. This allowed us to apply mechanical deformation to investigate the complex nature of cell shape and structure. These results will enhance our knowledge of cellular and molecular function as well as provide insights into fields including biomechanics, tissue engineering, and drug discovery.

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