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.

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

Development ◽  
2021 ◽  
Vol 148 (24) ◽  
Author(s):  
Megan K. Rommelfanger ◽  
Adam L. MacLean
Keyword(s):  
Cell Fate ◽  
Cell Communication ◽  
Communication Model ◽  
Cell Fate Decision ◽  
Cell Coupling ◽  
Environmental Signals ◽  
Cell Fate Decisions ◽  
Wide Range ◽  
Fate Decision ◽  
Cell Cell

ABSTRACT Cells do not make fate decisions independently. Arguably, every cell-fate decision occurs in response to environmental signals. In many cases, cell-cell communication alters the dynamics of the internal gene regulatory network of a cell to initiate cell-fate transitions, yet models rarely take this into account. Here, we have developed a multiscale perspective to study the granulocyte-monocyte versus megakaryocyte-erythrocyte fate decisions. This transition is dictated by the GATA1-PU.1 network: a classical example of a bistable cell-fate system. We show that, for a wide range of cell communication topologies, even subtle changes in signaling can have pronounced effects on cell-fate decisions. We go on to show how cell-cell coupling through signaling can spontaneously break the symmetry of a homogenous cell population. Noise, both intrinsic and extrinsic, shapes the decision landscape profoundly, and affects the transcriptional dynamics underlying this important hematopoietic cell-fate decision-making system. This article has an associated ‘The people behind the papers’ interview.

scholarly journals Fatty acyl donor selectivity in membrane bound O-acyltransferases and communal cell fate decision-making

2015 ◽  
Vol 43 (2) ◽  
pp. 235-239 ◽  
Author(s):  
Rubina Tuladhar ◽  
Lawrence Lum
Keyword(s):  
Decision Making ◽  
Cell Fate ◽  
Protein Function ◽  
Cell Communication ◽  
Fatty Acyl ◽  
Acyl Donor ◽  
Cell Fate Decision ◽  
Post Translational Modification ◽  
Membrane Bound ◽  
Fate Decision

The post-translational modification of proteins with lipid moieties confers spatial and temporal control of protein function by restricting their subcellular distribution or movement in the extracellular milieu. Yet, little is known about the significance of lipid selectivity to the activity of proteins targeted for such modifications. Membrane bound O-acyl transferases (MBOATs) are a superfamily of multipass enzymes that transfer fatty acids on to lipid or protein substrates. Three MBOATs constitute a subfamily with secreted signalling molecules for substrates, the Wnt, Hedgehog (Hh) and Ghrelin proteins. Given their important roles in adult tissue homoeostasis, all three molecules and their respective associated acyltransferases provide a framework for interrogating the role of extracellular acylation events in cell-to-cell communication. Here, we discuss how the preference for a fatty acyl donor in the Wnt acyltransferase porcupine (Porcn) and possibly in other protein lipidation enzymes may provide a means for coupling metabolic health at the single cell level to communal cell fate decision-making in complex multicellular organisms.

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 A hydraulic instability drives the cell death decision in the nematode germline

2020 ◽  
Author(s):  
N. T. Chartier ◽  
A. Mukherjee ◽  
J. Pfanzelter ◽  
S. Fürthauer ◽  
B. T. Larson ◽  
...  
Keyword(s):  
Decision Making ◽  
Cell Death ◽  
Cell Fate ◽  
Germ Cells ◽  
Cell Fate Decision ◽  
Homogeneous Population ◽  
C Elegans ◽  
The Common ◽  
Fate Decision ◽  
Cell Volumes

AbstractOocytes are large and resourceful. During oogenesis some germ cells grow, typically at the expense of others that undergo apoptosis. How germ cells are selected to live or die out of a homogeneous population remains unclear. Here we show that this cell fate decision in C. elegans is mechanical and related to tissue hydraulics. Germ cells become inflated when the pressure inside them is lower than in the common cytoplasmic pool. This condition triggers a hydraulic instability which amplifies volume differences and causes some germ cells to grow and others to shrink. Shrinking germ cells are extruded and die, as we demonstrate by reducing germ cell volumes via thermoviscous pumping. Together, this reveals a robust mechanism of mechanochemical cell fate decision making in the germline.

scholarly journals Wnt/B-catenin signalling facilitates cell fate decision making in the early mouse embryo

2017 ◽  
Vol 145 ◽  
pp. S159 ◽  
Author(s):  
Elena Corujo-Simon ◽  
Joaquin Lilao-Garzon ◽  
Silvia Muñoz-Descalzo
Keyword(s):  
Decision Making ◽  
Cell Fate ◽  
Mouse Embryo ◽  
Cell Fate Decision ◽  
Early Mouse Embryo ◽  
Fate Decision ◽  
Early Mouse

scholarly journals Uncertainty in cell fate decision making: Lessons from potential landscapes of bifurcation systems

2021 ◽  
Author(s):  
Anissa Guillemin ◽  
Elisabeth Roesch ◽  
Michael P.H. Stumpf
Keyword(s):  
Decision Making ◽  
Cell Fate ◽  
Qualitative Change ◽  
Pictorial Representation ◽  
Cell Fate Decision ◽  
Ample Evidence ◽  
Molecular Noise ◽  
Intrinsic Complexity ◽  
Fate Decision ◽  
The Stability

AbstractCell fate decision making is known to be a complex process and is still far from being understood. The intrinsic complexity, but also features such as molecular noise represent challenges for modelling these systems. Waddington’s epigenetic landscape has become the overriding metaphor for developmental processes: it both serves as pictorial representation, and can be related to mathematical models. In this work we investigate how the landscape is affected by noise in the underlying system. Specifically, we focus on those systems where minor changes in the parameters cause major changes in the stability properties of the system, especially bifurcations. We analyse and quantify the changes in the landscape’s shape as the effects of noise increase. We find ample evidence for intricate interplay between noise and dynamics which can lead to qualitative change in a system’s dynamics and hence the corresponding landscape. In particular, we find that the effects can be most pronounced in the vicinity of the bifurcation point of the underlying deterministic dynamical systems, which would correspond to the cell fate decision event in cellular differentiation processes.

scholarly journals Quantifying Waddington landscapes and paths of non-adiabatic cell fate decisions for differentiation, reprogramming and transdifferentiation

2013 ◽  
Vol 10 (89) ◽  
pp. 20130787 ◽  
Author(s):  
Chunhe Li ◽  
Jin Wang
Keyword(s):  
Decision Making ◽  
Stem Cell ◽  
Cell Fate ◽  
Intermediate State ◽  
Regulatory Networks ◽  
Experimental Studies ◽  
Cell Fate Decision ◽  
Cell Fate Decisions ◽  
Decision Making Processes ◽  
Fate Decision

Cellular differentiation, reprogramming and transdifferentiation are determined by underlying gene regulatory networks. Non-adiabatic regulation via slow binding/unbinding to the gene can be important in these cell fate decision-making processes. Based on a stem cell core gene network, we uncovered the stem cell developmental landscape. As the binding/unbinding speed decreases, the landscape topography changes from bistable attractors of stem and differentiated states to more attractors of stem and other different cell states as well as substates. Non-adiabaticity leads to more differentiated cell types and provides a natural explanation for the heterogeneity observed in the experiments. We quantified Waddington landscapes with two possible cell fate decision mechanisms by changing the regulation strength or regulation timescale (non-adiabaticity). Transition rates correlate with landscape topography through barrier heights between different states and quantitatively determine global stability. We found the optimal speeds of these cell fate decision-making processes. We quantified biological paths and predict that differentiation and reprogramming go through an intermediate state (IM1), whereas transdifferentiation goes through another intermediate state (IM2). Some predictions are confirmed by recent experimental studies.

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