scholarly journals Cell Fate Decision Making through Oriented Cell Division

2015 ◽  
Vol 3 (4) ◽  
pp. 129-157 ◽  
Author(s):  
Evan Dewey ◽  
Danielle Taylor ◽  
Christopher Johnston
Keyword(s):  
Decision Making ◽  
Cell Division ◽  
Cell Fate ◽  
Cell Fate Decision ◽  
Oriented Cell Division ◽  
Fate Decision

scholarly journals Cell fate clusters in ICM organoids arise from cell fate heredity and division: a modelling approach

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tim Liebisch ◽  
Armin Drusko ◽  
Biena Mathew ◽  
Ernst H. K. Stelzer ◽  
Sabine C. Fischer ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Division ◽  
Cell Fate ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Cell Lineage ◽  
Cell Fate Decision ◽  
Cell Fate Decisions ◽  
Chemical Signalling ◽  
Fate Decision

AbstractDuring the mammalian preimplantation phase, cells undergo two subsequent cell fate decisions. During the first decision, the trophectoderm and the inner cell mass are formed. Subsequently, the inner cell mass segregates into the epiblast and the primitive endoderm. Inner cell mass organoids represent an experimental model system, mimicking the second cell fate decision. It has been shown that cells of the same fate tend to cluster stronger than expected for random cell fate decisions. Three major processes are hypothesised to contribute to the cell fate arrangements: (1) chemical signalling; (2) cell sorting; and (3) cell proliferation. In order to quantify the influence of cell proliferation on the observed cell lineage type clustering, we developed an agent-based model accounting for mechanical cell–cell interaction, i.e. adhesion and repulsion, cell division, stochastic cell fate decision and cell fate heredity. The model supports the hypothesis that initial cell fate acquisition is a stochastically driven process, taking place in the early development of inner cell mass organoids. Further, we show that the observed neighbourhood structures can emerge solely due to cell fate heredity during cell division.

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.

Rho GTPase Activating Protein p190-B Regulates Hematopoietic Stem Cell Fate Decision

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 575-575
Author(s):  
Juying Xu ◽  
Kathleen Szczur ◽  
Haiming Xu ◽  
Hartmut Geiger ◽  
Yi Zheng ◽  
...  
Keyword(s):  
Cell Division ◽  
Cell Fate ◽  
Cell Shape ◽  
Rho Gtpase ◽  
Cell Fate Decision ◽  
Gtpase Activating Protein ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Fate Decision ◽  
Serial Transplantation

Abstract Abstract 575 Hematopoietic stem cells (HSC) are undifferentiated cells that are capable of self-renewal and production of all mature blood and immune cells. The molecular mechanisms that determine HSC self renewal and cell fate decision still remain poorly understood. We have previously shown that p190-B GTPase Activating Protein (GAP), a negative regulator of Rho activity, is a critical regulator of HSC self renewal. In these studies, while p190-B-deficiency did not alter HSC cell cycle kinetics or survival either in vivo and in vitro, the loss of p190-B conferred enhanced serial transplantation capacity and also preserved the repopulating capacity of HSC/Ps during ex vivo cytokine-induced culture compared to WT HSC/Ps. Together, these data suggest that p190-B modulates HSC self renewal decisions during cell division (Xu et al, Blood 2009). In the current study, we tested the hypothesis that p190-B modulates the balance of asymmetric/symmetric self renewal divisions. To do so, single LSK cells isolated from fetal livers were cultured in the presence of cytokines known to promote self renewal. After 1–2 divisions, the media was replaced with cytokines that promote both proliferation and differentiation. The kinetics of the first 1–2 divisions of WT and p190-B–/– LSK was similar (n=450). However, after 10 days, the size of clones derived from p190-B−/− LSK cells were larger. Importantly, the frequency of clones exhibiting multipotent lineage differentiation was also higher from p190-B−/− LSK compared with WT (18 multipotent clones out of 43 (42%) vs 10 out of 39 (26%)). Therefore, p190-B may modulate the balance of asymmetric/symmetric HSC self renewal divisions. One fundamental mechanism of asymmetric cell division is the asymmetric inheritance of cell fate determinants, which is controlled by the asymmetric distribution of the cytoskeleton and polarity cues. Because Rho GTPases are key regulators of cytoskeleton polarity, we next examined cell shape and polarity (of WT and p190-B–/– LSK cells). WT cells exhibited an asymmetric shape with two distinct cell poles, including one pole enriched with microtubules. In contrast, p190-B–/– LSK appeared round with a homogenous distribution of microtubules. Using image flow spectral analysis (Imagestream), we analyzed the distribution of numb, a conserved cell fate determinant, which is unequally distributed during stem cell division in order to generate distinct daughter cells. Significantly more p190-B–/– LSK showed a symmetric numb distribution than WT LSK (41±5.8% vs 29±4.6%, n>1000 cells from 3 independent experiments, p<0.02). To determine the importance of this cell shape change, we examined the p38MAPK signaling pathway, since p190-B is known to regulate p38MAPK activity (Sordella et al, Dev Cell 2002) and p38MAPK has been implicated HSC self renewal decision (Ito et al, Nat Med 2006). Flow cytometry analysis revealed that p38MAPK activity increased in WT LSK-CD150+ cells during serial transplantation. p190-B-deficiency prevents the elevation of p38MAPK activity in HSC in secondary transplant recipients (mean fluorescence intensity in HSC isolated from non transplanted animals: 1182±439; from secondary recipients of WT HSC: 2218±680=; from secondary recipients of p190-B−/− HSC: 1540±711**, n=7, *p<0.01 compared to non transplanted mice; ** p<0.01 compared to WT and ns compared to non transplanted mice). Remarkably, inhibition of p38MAPK activity in WT LSK led to alterations in shape and polarity that was similar to p190-B–/– LSK. Furthermore, p38MAPK inhibition significantly increased LSK competitive repopulation activity after 7 days in culture, compared to vehicle treated LSK cells (chimera 53±1.7 vs 23±18%, n=4, p<0.02). Together, these data suggest that p190-B regulates HSC/P self renewal by modulating cell fate decision as the cell divide and that HSC/P shape integrity is critical for this process. This study implies that modulating cell polarity via Rho GTPase may provide rational to devise new therapeutic approaches to clinical HSC transplantation protocols. Disclosures: Filippi: American Heart Association: Research Funding.

scholarly journals Insights into the molecular mechanisms of cell fate decision making processes from chromosome structural dynamics

2021 ◽  
Author(s):  
Xiakun Chu ◽  
Jin Wang
Keyword(s):  
Decision Making ◽  
Cell Fate ◽  
Structural Dynamics ◽  
Normal Cell ◽  
Molecular Mechanisms ◽  
State Transitions ◽  
Cell Fate Decision ◽  
Cell State ◽  
Decision Making Processes ◽  
Fate Decision

Cell state transitions or cell fate decision making processes, such as cell development and cell pathological transformation, are believed to be determined by the regulatory network of genes, which intimately depend on the structures of chromosomes in the cell nucleus. The high temporal resolution picture of how chromosome reorganizes its 3D structure during the cell state transitions is the key to understanding the mechanisms of these fundamental cellular processes. However, this picture is still challenging to acquire at present. Here, we studied the chromosome structural dynamics during the cell state transitions among the pluripotent embryonic stem cell (ESC), the terminally differentiated normal cell and the cancer cell using landscape-switching model implemented in the molecular dynamics simulation. We considered up to 6 transitions, including differentiation, reprogramming, cancer formation and reversion. We found that the pathways can merge at certain stages during the transitions for the two processes having the same destination as the ESC or the normal cell. Before reaching the merging point, the two pathways are cell-type-specific. The chromosomes at the merging points show high structural similarity to the ones at the final cell states in terms of the contact maps, TADs and compartments. The post-merging processes correspond to the adaption of the chromosome global shape geometry through the chromosome compaction without significantly disrupting the contact formation. On the other hand, our detailed analysis showed no merging point for the two cancer formation processes initialized from the ESC and the normal cell, implying that cancer progression is a complex process and may be associated with multiple pathways. Our results draw a complete molecular picture of cell development and cancer at the dynamical chromosome structural level, and help our understanding of the molecular mechanisms of cell fate decision making processes.

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