scholarly journals Keeping your options open: insights from Dppa2/4 into how epigenetic priming factors promote cell plasticity

2020 ◽  
Vol 48 (6) ◽  
pp. 2891-2902
Author(s):  
Mélanie A. Eckersley-Maslin
Keyword(s):  
Cell Fate ◽  
Regulatory Elements ◽  
Cell Plasticity ◽  
Cell Identity ◽  
Transcriptional Changes ◽  
A Cell ◽  
The Stability ◽  
External Stimuli ◽  
Epigenetic Plasticity

The concept of cellular plasticity is particularly apt in early embryonic development, where there is a tug-of-war between the stability and flexibility of cell identity. This balance is controlled in part through epigenetic mechanisms. Epigenetic plasticity dictates how malleable cells are to change by adjusting the potential to initiate new transcriptional programmes. The higher the plasticity of a cell, the more readily it can adapt and change its identity in response to external stimuli such as differentiation cues. Epigenetic plasticity is regulated in part through the action of epigenetic priming factors which establish this permissive epigenetic landscape at genomic regulatory elements to enable future transcriptional changes. Recent studies on the DNA binding proteins Developmental Pluripotency Associated 2 and 4 (Dppa2/4) support their roles as epigenetic priming factors in facilitating cell fate transitions. Here, using Dppa2/4 as a case study, the concept of epigenetic plasticity and molecular mechanism of epigenetic priming factors will be explored. Understanding how epigenetic priming factors function is key not only to improve our understanding of the tight control of development, but also to give insights into how this goes awry in diseases of cell identity, such as cancer.

scholarly journals Genome Architecture Leads a Bifurcation in Cell Identity

2017 ◽  
Author(s):  
Sijia Liu ◽  
Haiming Chen ◽  
Scott Ronquist ◽  
Laura Seaman ◽  
Nicholas Ceglia ◽  
...  
Keyword(s):  
Cell Fate ◽  
Human Fibroblasts ◽  
Biological Rhythms ◽  
System Level ◽  
Genome Architecture ◽  
Cell Identity ◽  
Cell Therapies ◽  
A Cell ◽  
Fate Decision ◽  
Myogenic Program

SUMMARYGenome architecture is important in transcriptional regulation and study of its features is a critical part of fully understanding cell identity. Altering cell identity is possible through overexpression of transcription factors (TFs); for example, fibroblasts can be reprogrammed into muscle cells by introducing MYOD1. How TFs dynamically orchestrate genome architecture and transcription as a cell adopts a new identity during reprogramming is not well understood. Here we show that MYOD1-mediated reprogramming of human fibroblasts into the myogenic lineage undergoes a critical transition, which we refer to as a bifurcation point, where cell identity definitively changes. By integrating knowledge of genome-wide dynamical architecture and transcription, we found significant chromatin reorganization prior to transcriptional changes that marked activation of the myogenic program. We also found that the local architectural and transcriptional dynamics of endogenous MYOD1 and MYOG reflected the global genomic bifurcation event. These TFs additionally participate in entrainment of biological rhythms. Understanding the system-level genome dynamics underlying a cell fate decision is a step toward devising more sophisticated reprogramming strategies that could be used in cell therapies.

scholarly journals The transcriptional corepressor CTBP-1 acts with the SOX family transcription factor EGL-13 to maintain AIA interneuron cell identity in C. elegans

2021 ◽  
Author(s):  
Josh Saul ◽  
Takashi Hirose ◽  
Robert Horvitz
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Cell Fate ◽  
Transcriptional Corepressor ◽  
Cell Identity ◽  
C Elegans ◽  
Dna Binding Specificity ◽  
A Cell ◽  
Transcriptional Corepressors ◽  
And Function

Cell identity is characterized by a distinct combination of gene expression, cell morphology and cellular function established as progenitor cells divide and differentiate. Following establishment, cell identities can be unstable and require active and continuous maintenance throughout the remaining life of a cell. Mechanisms underlying the maintenance of cell identities are incompletely understood. Here we show that the gene ctbp-1, which encodes the transcriptional corepressor C-terminal binding protein-1 (CTBP-1), is essential for the maintenance of the identities of the two AIA interneurons in the nematode Caenorhabditis elegans. ctbp-1 is not required for the establishment of the AIA cell fate but rather functions cell-autonomously and can act in older worms to maintain proper AIA gene expression, morphology and function. From a screen for suppressors of the ctbp-1 mutant phenotype, we identified the gene egl-13, which encodes a SOX family transcription factor. We found that egl-13 regulates AIA function and aspects of AIA gene expression, but not AIA morphology. We conclude that the CTBP-1 protein maintains AIA cell identity in part by utilizing EGL-13 to repress transcriptional activity in the AIAs. More generally, we propose that transcriptional corepressors like CTBP-1 might be critical factors in the maintenance of cell identities, harnessing the DNA-binding specificity of transcription factors like EGL-13 to selectively regulate gene expression in a cell-specific manner.

scholarly journals A single cell Arabidopsis root atlas reveals developmental trajectories in wild type and cell identity mutants

2020 ◽  
Author(s):  
Rachel Shahan ◽  
Che-Wei Hsu ◽  
Trevor M. Nolan ◽  
Benjamin J. Cole ◽  
Isaiah W. Taylor ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Developmental Process ◽  
Developmental Trajectories ◽  
Alternative Pathway ◽  
Lineage Tracing ◽  
Sequencing Data ◽  
Cell Identity ◽  
Developmental States ◽  
A Cell

SummaryCell fate acquisition is a fundamental developmental process in all multicellular organisms. Yet, much is unknown regarding how a cell traverses the pathway from stem cell to terminal differentiation. Advances in single cell genomics1 hold promise for unraveling developmental mechanisms2–3 in tissues4, organs5–6, and organisms7–8. However, lineage tracing can be challenging for some tissues9 and integration of high-quality datasets is often necessary to detect rare cell populations and developmental states10,11. Here, we harmonized single cell mRNA sequencing data from over 110,000 cells to construct a comprehensive atlas for a stereotypically developing organ with indeterminate growth, the Arabidopsis root. To test the utility of the atlas to interpret new datasets, we profiled mutants for two key transcriptional regulators at single cell resolution, shortroot and scarecrow. Although both transcription factors are required for early specification of cell identity12, our results suggest the existence of an alternative pathway acting in mature cells to specify endodermal identity, for which SHORTROOT is required. Uncovering the architecture of this pathway will provide insight into specification and stabilization of the endodermis, a tissue analogous to the mammalian epithelium. Thus, the atlas is a pivotal advance for unraveling the transcriptional programs that specify and maintain cell identity to regulate organ development in space and time.

scholarly journals UPMaBoSS: a novel framework for dynamic cell population modeling

2020 ◽  
Author(s):  
Gautier Stoll ◽  
Aurélien Naldi ◽  
Vincent Noël ◽  
Eric Viara ◽  
Emmanuel Barillot ◽  
...  
Keyword(s):  
Population Dynamics ◽  
Cell Fate ◽  
Cellular Networks ◽  
Cell Population ◽  
Cell Fate Decisions ◽  
Dynamic Cell ◽  
Drug Treatments ◽  
A Cell ◽  
The Impact

AbstractOne of the aims of mathematical modeling is to understand and simulate the effects of biological perturbations and suggest ways to intervene and reestablish proper cell functioning. However, it remains a challenge, especially when considering the dynamics at the level of a cell population, with cells dying, dividing and interacting. Here, we introduce a novel framework for the dynamical modelling of cell populations packaged into a dedicated tool, UPMaBoSS. We rely on the preexisting tool MaBoSS, which enables probabilistic simulations of cellular networks, and add a novel layer to account for cell interactions and population dynamics. We illustrate our methodology by means of a case study dealing with TNF-induced cell death. Interestingly, the simulation of cell population dynamics with UPMaBoSS reveals a mechanism of resistance triggered by TNF treatment. This appoach can be applied to diverse models of cellular networks, for example to study the impact of ligand release or drug treatments on cell fate decisions, such as commitment to proliferation, differentiation, apoptosis, etc. Relatively easy to encode, UPMaBoSS simulations require only moderate computational power and execution time.To ease the reproduction of simulations, we provide several Jupyter notebooks that can be accessed within a new release of the CoLoMoTo Docker image, which contains all required software and the example models.

Using FRET to Measure the Time it Takes for a Cell to Destroy a Virus

2019 ◽  
Author(s):  
Candace E. Benjamin ◽  
Zhuo Chen ◽  
Olivia Brohlin ◽  
Hamilton Lee ◽  
Stefanie Boyd ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Rhodamine B ◽  
Virus Like Particle ◽  
A Cell ◽  
Viral Nanoparticles ◽  
The Stability ◽  
Open Question ◽  
Viral Surface ◽  
Fret Pair

<div><div><div><p>The emergence of viral nanotechnology over the preceding two decades has created a number of intellectually captivating possible translational applications; however, the in vitro fate of the viral nanoparticles in cells remains an open question. Herein, we investigate the stability and lifetime of virus-like particle (VLP) Qβ - a representative and popular VLP for several applications - following cellular uptake. By exploiting the available functional handles on the viral surface, we have orthogonally installed the known FRET pair, FITC and Rhodamine B, to gain insight of the particle’s behavior in vitro. Based on these data, we believe VLPs undergo aggregation in addition to the anticipated proteolysis within a few hours of cellular uptake.</p></div></div></div>

Applications of random graphs

2017 ◽  
Author(s):  
A.C.C. Coolen ◽  
A. Annibale ◽  
E.S. Roberts
Keyword(s):  
Social Networks ◽  
Random Graphs ◽  
Interaction Network ◽  
Power Grids ◽  
Protein Protein Interaction ◽  
Topological Features ◽  
First Case ◽  
The Stability ◽  
Protein Protein Interaction Network

This chapter reviews graph generation techniques in the context of applications. The first case study is power grids, where proposed strategies to prevent blackouts have been tested on tailored random graphs. The second case study is in social networks. Applications of random graphs to social networks are extremely wide ranging – the particular aspect looked at here is modelling the spread of disease on a social network – and how a particular construction based on projecting from a bipartite graph successfully captures some of the clustering observed in real social networks. The third case study is on null models of food webs, discussing the specific constraints relevant to this application, and the topological features which may contribute to the stability of an ecosystem. The final case study is taken from molecular biology, discussing the importance of unbiased graph sampling when considering if motifs are over-represented in a protein–protein interaction network.

Supplier Development at LG Electronics

2020 ◽  
Author(s):  
Hyojin Kim ◽  
Daesik Hur ◽  
Tobias Schoenherr
Keyword(s):  
Management Practice ◽  
Digital Technologies ◽  
Supply Management ◽  
Future Research ◽  
Supplier Development ◽  
Environmentally Conscious ◽  
Competitive Capabilities ◽  
The Stability ◽  
Buyer Firm

Supplier development has been a critical supply management practice since the 1990s. In many instances, it has even become imperative for buyer firms to support and prepare their supply bases for uncertain economic and market environments, socially and environmentally conscious customers, advances in digital technologies, and increasing competition. Yet, research that approaches supplier development with the objective to advance all these dimensions in an integrated fashion is scarce. This study fills this void by exploring how a buyer firm may address these emerging challenges in its supply base. Specifically, an in-depth case study of LG Electronics explores how the firm designs and operates multidimensional supplier development activities to foster the stability and sustainability of its supply base while enhancing its core suppliers’ competitive capabilities. This chapter illustrates how supplier development can be taken to the next level, presents implications for managerial practice, and outlines promising future research avenues.

scholarly journals Cadherins in early neural development

2021 ◽  
Author(s):  
Karolina Punovuori ◽  
Mattias Malaguti ◽  
Sally Lowell
Keyword(s):  
Adhesion Molecules ◽  
Cell Fate ◽  
Neural Development ◽  
Ex Vivo ◽  
Directed Differentiation ◽  
Culture Dish ◽  
Cell Identity ◽  
Cell Fate Decisions ◽  
Neural Tissues ◽  
And Function

AbstractDuring early neural development, changes in signalling inform the expression of transcription factors that in turn instruct changes in cell identity. At the same time, switches in adhesion molecule expression result in cellular rearrangements that define the morphology of the emerging neural tube. It is becoming increasingly clear that these two processes influence each other; adhesion molecules do not simply operate downstream of or in parallel with changes in cell identity but rather actively feed into cell fate decisions. Why are differentiation and adhesion so tightly linked? It is now over 60 years since Conrad Waddington noted the remarkable "Constancy of the Wild Type” (Waddington in Nature 183: 1654–1655, 1959) yet we still do not fully understand the mechanisms that make development so reproducible. Conversely, we do not understand why directed differentiation of cells in a dish is sometimes unpredictable and difficult to control. It has long been suggested that cells make decisions as 'local cooperatives' rather than as individuals (Gurdon in Nature 336: 772–774, 1988; Lander in Cell 144: 955–969, 2011). Given that the cadherin family of adhesion molecules can simultaneously influence morphogenesis and signalling, it is tempting to speculate that they may help coordinate cell fate decisions between neighbouring cells in the embryo to ensure fidelity of patterning, and that the uncoupling of these processes in a culture dish might underlie some of the problems with controlling cell fate decisions ex-vivo. Here we review the expression and function of cadherins during early neural development and discuss how and why they might modulate signalling and differentiation as neural tissues are formed.

scholarly journals The Temporal Order of DNA Replication Shaped by Mammalian DNA Methyltransferases

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 266
Author(s):  
Shin-ichiro Takebayashi ◽  
Tyrone Ryba ◽  
Kelsey Wimbish ◽  
Takuya Hayakawa ◽  
Morito Sakaue ◽  
...  
Keyword(s):  
Dna Replication ◽  
Temporal Order ◽  
Expression System ◽  
Embryonic Stem ◽  
Replication Timing ◽  
Dna Methyltransferases ◽  
Dna Hypomethylation ◽  
Transcriptional Changes ◽  
A Cell ◽  
Genomic Regions

Multiple epigenetic pathways underlie the temporal order of DNA replication (replication timing) in the contexts of development and disease. DNA methylation by DNA methyltransferases (Dnmts) and downstream chromatin reorganization and transcriptional changes are thought to impact DNA replication, yet this remains to be comprehensively tested. Using cell-based and genome-wide approaches to measure replication timing, we identified a number of genomic regions undergoing subtle but reproducible replication timing changes in various Dnmt-mutant mouse embryonic stem (ES) cell lines that included a cell line with a drug-inducible Dnmt3a2 expression system. Replication timing within pericentromeric heterochromatin (PH) was shown to be correlated with redistribution of H3K27me3 induced by DNA hypomethylation: Later replicating PH coincided with H3K27me3-enriched regions. In contrast, this relationship with H3K27me3 was not evident within chromosomal arm regions undergoing either early-to-late (EtoL) or late-to-early (LtoE) switching of replication timing upon loss of the Dnmts. Interestingly, Dnmt-sensitive transcriptional up- and downregulation frequently coincided with earlier and later shifts in replication timing of the chromosomal arm regions, respectively. Our study revealed the previously unrecognized complex and diverse effects of the Dnmts loss on the mammalian DNA replication landscape.

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