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Stochasticity of cellular differentiation

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https://www.readbyqxmd.com/read/28799233/stochastics-of-cellular-differentiation-explained-by-epigenetics-the-case-of-t-cell-differentiation-and-functional-plasticity
#1
REVIEW
Jaydeep Bhat, Johannes Helmuth, Guranda Chitadze, Léonce Kouakanou, Christian Peters, Martin Vingron, Ole Ammerpohl, Dieter Kabelitz
Epigenetic marks including histone modifications and DNA methylation are associated to the regulation of gene expression and activity. In addition, an increasing number of non-coding RNAs with regulatory activity on gene expression have been identified. Alongside, technological advancements allow for the analysis of these mechanisms with high resolution - up to the single-cell level. For instance, the assay for transposase-accessible chromatin using sequencing (ATAC-seq) simultaneously probes for chromatin accessibility and nucleosome positioning...
August 10, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28729483/epigenetic-plasticity-and-the-hallmarks-of-cancer
#2
REVIEW
William A Flavahan, Elizabeth Gaskell, Bradley E Bernstein
Chromatin and associated epigenetic mechanisms stabilize gene expression and cellular states while also facilitating appropriate responses to developmental or environmental cues. Genetic, environmental, or metabolic insults can induce overly restrictive or overly permissive epigenetic landscapes that contribute to pathogenesis of cancer and other diseases. Restrictive chromatin states may prevent appropriate induction of tumor suppressor programs or block differentiation. By contrast, permissive or "plastic" states may allow stochastic oncogene activation or nonphysiologic cell fate transitions...
July 21, 2017: Science
https://www.readbyqxmd.com/read/28724976/gene-expression-reversal-toward-pre-adult-levels-in-the-aging-human-brain-and-age-related-loss-of-cellular-identity
#3
Handan Melike Dönertaş, Hamit İzgi, Altuğ Kamacıoğlu, Zhisong He, Philipp Khaitovich, Mehmet Somel
It was previously reported that mRNA expression levels in the prefrontal cortex at old age start to resemble pre-adult levels. Such expression reversals could imply loss of cellular identity in the aging brain, and provide a link between aging-related molecular changes and functional decline. Here we analyzed 19 brain transcriptome age-series datasets, comprising 17 diverse brain regions, to investigate the ubiquity and functional properties of expression reversal in the human brain. Across all 19 datasets, 25 genes were consistently up-regulated during postnatal development and down-regulated in aging, displaying an "up-down" pattern that was significant as determined by random permutations...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28714002/identification-of-key-genes-in-gram%C3%A2-positive-and-gram%C3%A2-negative-sepsis-using-stochastic-perturbation
#4
Zhenliang Li, Ying Zhang, Yaling Liu, Yanchun Liu, Youyi Li
Sepsis is an inflammatory response to pathogens (such as Gram‑positive and Gram‑negative bacteria), which has high morbidity and mortality in critically ill patients. The present study aimed to identify the key genes in Gram‑positive and Gram‑negative sepsis. GSE6535 was downloaded from Gene Expression Omnibus, containing 17 control samples, 18 Gram‑positive samples and 25 Gram‑negative samples. Subsequently, the limma package in R was used to screen the differentially expressed genes (DEGs). Hierarchical clustering was conducted for the specific DEGs in Gram‑negative and Gram‑negative samples using cluster software and the TreeView software...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28669884/determining-the-control-networks-regulating-stem-cell-lineages-in-colonic-crypts
#5
Jienian Yang, David E Axelrod, Natalia L Komarova
The question of stem cell control is at the center of our understanding of tissue functioning, both in healthy and cancerous conditions. It is well accepted that cellular fate decisions (such as divisions, differentiation, apoptosis) are orchestrated by a network of regulatory signals emitted by different cell populations in the lineage and the surrounding tissue. The exact regulatory network that governs stem cell lineages in a given tissue is usually unknown. Here we propose an algorithm to identify a set of candidate control networks that are compatible with (a) measured means and variances of cell populations in different compartments, (b) qualitative information on cell population dynamics, such as the existence of local controls and oscillatory reaction of the system to population size perturbations, and (c) statistics of correlations between cell numbers in different compartments...
September 21, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28597056/a-space-jump-derivation-for-non-local-models-of-cell-cell-adhesion-and-non-local-chemotaxis
#6
Andreas Buttenschön, Thomas Hillen, Alf Gerisch, Kevin J Painter
Cellular adhesion provides one of the fundamental forms of biological interaction between cells and their surroundings, yet the continuum modelling of cellular adhesion has remained mathematically challenging. In 2006, Armstrong et al. proposed a mathematical model in the form of an integro-partial differential equation. Although successful in applications, a derivation from an underlying stochastic random walk has remained elusive. In this work we develop a framework by which non-local models can be derived from a space-jump process...
June 8, 2017: Journal of Mathematical Biology
https://www.readbyqxmd.com/read/28573304/universal-signal-generator-for-dynamic-cell-stimulation
#7
Andreas Piehler, Navid Ghorashian, Ce Zhang, Savaş Tay
Dynamic cell stimulation is a powerful technique for probing gene networks and for applications in stem cell differentiation, immunomodulation and signaling. We developed a robust and flexible method and associated microfluidic devices to generate a wide-range of precisely formulated dynamic chemical signals to stimulate live cells and measure their dynamic response. This signal generator is capable of digital to analog conversion (DAC) through combinatoric selection of discrete input concentrations, and outperforms existing methods by both achievable resolution, dynamic range and simplicity in design...
June 2, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28536035/seasonality-can-induce-coexistence-of-multiple-bet-hedging-strategies-in-dictyostelium-discoideum-via-storage-effect
#8
Ricardo Martínez-García, Corina E Tarnita
The social amoeba Dictyostelium discoideum has been recently suggested as an example of bet-hedging in microbes. In the presence of resources, amoebae reproduce as unicellular organisms. Resource depletion, however, leads to a starvation phase in which the population splits between aggregators, which form a fruiting body made of a stalk and resistant spores, and non-aggregators, which remain as vegetative cells. Spores are favored when starvation periods are long, but vegetative cells can exploit resources in environments where food replenishes quickly...
May 20, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28529938/senescence-inflammatory-regulation-of-reparative-cellular-reprogramming-in-aging-and-cancer
#9
Javier A Menendez, Tomás Alarcón
The inability of adult tissues to transitorily generate cells with functional stem cell-like properties is a major obstacle to tissue self-repair. Nuclear reprogramming-like phenomena that induce a transient acquisition of epigenetic plasticity and phenotype malleability may constitute a reparative route through which human tissues respond to injury, stress, and disease. However, tissue rejuvenation should involve not only the transient epigenetic reprogramming of differentiated cells, but also the committed re-acquisition of the original or alternative committed cell fate...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28521011/translation-initiation-events-on-structured-eukaryotic-mrnas-generate-gene-expression-noise
#10
Estelle Dacheux, Naglis Malys, Xiang Meng, Vinoy Ramachandran, Pedro Mendes, John Eg McCarthy
Gene expression stochasticity plays a major role in biology, creating non-genetic cellular individuality and influencing multiple processes, including differentiation and stress responses. We have addressed the lack of knowledge about posttranscriptional contributions to noise by determining cell-to-cell variations in the abundance of mRNA and reporter protein in yeast. Two types of structural element, a stem-loop and a poly(G) motif, not only inhibit translation initiation when inserted into an mRNA 5΄ untranslated region, but also generate noise...
May 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28511648/a-mathematical-model-of-mechanotransduction-reveals-how-mechanical-memory-regulates-mesenchymal-stem-cell-fate-decisions
#11
Tao Peng, Linan Liu, Adam L MacLean, Chi Wut Wong, Weian Zhao, Qing Nie
BACKGROUND: Mechanical and biophysical properties of the cellular microenvironment regulate cell fate decisions. Mesenchymal stem cell (MSC) fate is influenced by past mechanical dosing (memory), but the mechanisms underlying this process have not yet been well defined. We have yet to understand how memory affects specific cell fate decisions, such as the differentiation of MSCs into neurons, adipocytes, myocytes, and osteoblasts. RESULTS: We study a minimal gene regulatory network permissive of multi-lineage MSC differentiation into four cell fates...
May 16, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28379629/characterization-of-plasma-membrane-ceramides-by-super-resolution-microscopy
#12
Anne Burgert, Jan Schlegel, Jérôme Bécam, Sören Doose, Erhard Bieberich, Alexandra Schubert-Unkmeir, Markus Sauer
The sphingolipid ceramide regulates cellular processes such as differentiation, proliferation, growth arrest, and apoptosis. Ceramide-rich membrane areas promote structural changes within the plasma membrane that segregate membrane receptors and affect membrane curvature and vesicle formation, fusion, and trafficking. Ceramides were labeled by immunocytochemistry to visualize their distribution on the plasma membrane of different cells with virtually molecular resolution by direct stochastic optical reconstruction microscopy (dSTORM)...
May 22, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28379537/tasic-determining-branching-models-from-time-series-single-cell-data
#13
Sabrina Rashid, Darrell N Kotton, Ziv Bar-Joseph
Motivation: Single cell RNA-Seq analysis holds great promise for elucidating the networks and pathways controlling cellular differentiation and disease. However, the analysis of time series single cell RNA-Seq data raises several new computational challenges. Cells at each time point are often sampled from a mixture of cell types, each of which may be a progenitor of one, or several, specific fates making it hard to determine which cells should be used to reconstruct temporal trajectories...
August 15, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28325918/robust-analysis-of-fluxes-in-genome-scale-metabolic-pathways
#14
Michael MacGillivray, Amy Ko, Emily Gruber, Miranda Sawyer, Eivind Almaas, Allen Holder
Constraint-based optimization, such as flux balance analysis (FBA), has become a standard systems-biology computational method to study cellular metabolisms that are assumed to be in a steady state of optimal growth. The methods are based on optimization while assuming (i) equilibrium of a linear system of ordinary differential equations, and (ii) deterministic data. However, the steady-state assumption is biologically imperfect, and several key stoichiometric coefficients are experimentally inferred from situations of inherent variation...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28319730/deconstructing-the-germinal-center-one-cell-at-a-time
#15
REVIEW
Chad R Dufaud, Louise J McHeyzer-Williams, Michael G McHeyzer-Williams
Successful vaccination relies on driving the immune response towards high specificity, affinity and longevity. Germinal centers facilitate the evolution of antigen-specific B cells by iterative rounds of diversification, selection, and differentiation to memory and plasma cells. Experimental evidence points to B cell receptor affinity and amount of antigen presented to follicular helper T cells as main drivers of clonal evolution. Concurrent studies suggest that modifiers of cognate contact, temporal mechanisms, and stochastic factors can also shape diversity and influence differentiation to memory and plasma cells, but molecular pathways driving these selection decisions are unresolved...
April 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28219439/rnas-competing-for-micrornas-mutually-influence-their-fluctuations-in-a-highly-non-linear-microrna-dependent-manner-in-single-cells
#16
Carla Bosia, Francesco Sgrò, Laura Conti, Carlo Baldassi, Davide Brusa, Federica Cavallo, Ferdinando Di Cunto, Emilia Turco, Andrea Pagnani, Riccardo Zecchina
BACKGROUND: Distinct RNA species may compete for binding to microRNAs (miRNAs). This competition creates an indirect interaction between miRNA targets, which behave as miRNA sponges and eventually influence each other's expression levels. Theoretical predictions suggest that not only the mean expression levels of targets but also the fluctuations around the means are coupled through miRNAs. This may result in striking effects on a broad range of cellular processes, such as cell differentiation and proliferation...
February 20, 2017: Genome Biology
https://www.readbyqxmd.com/read/28202515/systematic-in-vivo-inactivation-of-chromatin-regulating-enzymes-identifies-setd2-as-a-potent-tumor-suppressor-in-lung-adenocarcinoma
#17
David M Walter, Olivia S Venancio, Elizabeth L Buza, John W Tobias, Charuhas Deshpande, A Andrea Gudiel, Caroline Kim-Kiselak, Michelle Cicchini, Travis J Yates, David M Feldser
Chromatin-modifying genes are frequently mutated in human lung adenocarcinoma, but the functional impact of these mutations on disease initiation and progression is not well understood. Using a CRISPR-based approach, we systematically inactivated three of the most commonly mutated chromatin regulatory genes in two Kras(G12D)-driven mouse models of lung adenocarcinoma to characterize the impact of their loss. Targeted inactivation of SWI/SNF nucleosome-remodeling complex members Smarca4 (Brg1) or Arid1a had complex effects on lung adenocarcinoma initiation and progression...
April 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28178232/synthetic-vulnerabilities-of-mesenchymal-subpopulations-in-pancreatic-cancer
#18
Giannicola Genovese, Alessandro Carugo, James Tepper, Frederick Scott Robinson, Liren Li, Maria Svelto, Luigi Nezi, Denise Corti, Rosalba Minelli, Piergiorgio Pettazzoni, Tony Gutschner, Chia-Chin Wu, Sahil Seth, Kadir Caner Akdemir, Elisabetta Leo, Samirkumar Amin, Marco Dal Molin, Haoqiang Ying, Lawrence N Kwong, Simona Colla, Koichi Takahashi, Papia Ghosh, Virginia Giuliani, Florian Muller, Prasenjit Dey, Shan Jiang, Jill Garvey, Chang-Gong Liu, Jianhua Zhang, Timothy P Heffernan, Carlo Toniatti, Jason B Fleming, Michael G Goggins, Laura D Wood, Alessandro Sgambato, Abbas Agaimy, Anirban Maitra, Charles W M Roberts, Huamin Wang, Andrea Viale, Ronald A DePinho, Giulio F Draetta, Lynda Chin
Malignant neoplasms evolve in response to changes in oncogenic signalling. Cancer cell plasticity in response to evolutionary pressures is fundamental to tumour progression and the development of therapeutic resistance. Here we determine the molecular and cellular mechanisms of cancer cell plasticity in a conditional oncogenic Kras mouse model of pancreatic ductal adenocarcinoma (PDAC), a malignancy that displays considerable phenotypic diversity and morphological heterogeneity. In this model, stochastic extinction of oncogenic Kras signalling and emergence of Kras-independent escaper populations (cells that acquire oncogenic properties) are associated with de-differentiation and aggressive biological behaviour...
February 16, 2017: Nature
https://www.readbyqxmd.com/read/28135279/cell-sorting-and-noise-induced-cell-plasticity-coordinate-to-sharpen-boundaries-between-gene-expression-domains
#19
Qixuan Wang, William R Holmes, Julian Sosnik, Thomas Schilling, Qing Nie
A fundamental question in biology is how sharp boundaries of gene expression form precisely in spite of biological variation/noise. Numerous mechanisms position gene expression domains across fields of cells (e.g. morphogens), but how these domains are refined remains unclear. In some cases, domain boundaries sharpen through differential adhesion-mediated cell sorting. However, boundaries can also sharpen through cellular plasticity, with cell fate changes driven by up- or down-regulation of gene expression...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28129434/development-of-an-in-silico-stochastic-4d-model-of-tumor-growth-with-angiogenesis
#20
Jake C Forster, Michael J J Douglass, Wendy M Harriss-Phillips, Eva Bezak
PURPOSE: A stochastic computer model of tumour growth with spatial and temporal components that includes tumour angiogenesis was developed. In the current work it was used to simulate head and neck tumour growth. The model also provides the foundation for a 4D cellular radiotherapy simulation tool. METHODS: The model, developed in Matlab, contains cell positions randomised in 3D space without overlap. Blood vessels are represented by strings of blood vessel units which branch outwards to achieve the desired tumour relative vascular volume...
April 2017: Medical Physics
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