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Stochasticity of cellular differentiation

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https://www.readbyqxmd.com/read/29119506/complexity-of-biochemical-and-genetic-responses-reduced-using-simple-theoretical-models
#1
Kumar Selvarajoo
Living systems are known to behave in a complex and sometimes unpredictable manner. Humans, for a very long time, have been intrigued by nature, and have attempted to understand biological processes and mechanisms using numerous experimental and mathematical techniques. In this chapter, we will look at simple theoretical models, using both linear and nonlinear differential equations, that realistically capture complex biochemical and genetic responses of living cells. Even for cases where cellular behaviors are stochastic, as for single-cell responses, randomness added to well-defined deterministic models has elegantly been shown to be useful...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29058744/hybrid-deterministic-stochastic-simulation-of-complex-biochemical-systems
#2
Paola Lecca, Fabio Bagagiolo, Marina Scarpa
In a biological cell, cellular functions and the genetic regulatory apparatus are implemented and controlled by complex networks of chemical reactions involving genes, proteins, and enzymes. Accurate computational models are indispensable means for understanding the mechanisms behind the evolution of a complex system, not always explored with wet lab experiments. To serve their purpose, computational models, however, should be able to describe and simulate the complexity of a biological system in many of its aspects...
October 23, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/29030469/single-cell-gene-expression-analysis-reveals-regulators-of-distinct-cell-subpopulations-among-developing-human-neurons
#3
Jiaxu Wang, Piroon Jenjaroenpun, Akshay Bhinge, Vladimir Espinosa Angarica, Antonio Del Sol, Intawat Nookaew, Vladimir A Kuznetsov, Lawrence W Stanton
The stochastic dynamics and regulatory mechanisms that govern differentiation of individual human neural precursor cells (NPC) into mature neurons are currently not fully understood. Here, we used single-cell RNA-sequencing (scRNA-seq) of developing neurons to dissect/identify NPC subtypes and critical developmental stages of alternative lineage specifications. This study comprises an unsupervised, high-resolution strategy for identifying cell developmental bifurcations, tracking the stochastic transcript kinetics of the subpopulations, elucidating regulatory networks, and finding key regulators...
November 2017: Genome Research
https://www.readbyqxmd.com/read/28981626/mathematical-modeling-and-computational-prediction-of-cancer-drug-resistance
#4
Xiaoqiang Sun, Bin Hu
Diverse forms of resistance to anticancer drugs can lead to the failure of chemotherapy. Drug resistance is one of the most intractable issues for successfully treating cancer in current clinical practice. Effective clinical approaches that could counter drug resistance by restoring the sensitivity of tumors to the targeted agents are urgently needed. As numerous experimental results on resistance mechanisms have been obtained and a mass of high-throughput data has been accumulated, mathematical modeling and computational predictions using systematic and quantitative approaches have become increasingly important, as they can potentially provide deeper insights into resistance mechanisms, generate novel hypotheses or suggest promising treatment strategies for future testing...
June 23, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28957659/stem-cell-differentiation-as-a-non-markov-stochastic-process
#5
Patrick S Stumpf, Rosanna C G Smith, Michael Lenz, Andreas Schuppert, Franz-Josef Müller, Ann Babtie, Thalia E Chan, Michael P H Stumpf, Colin P Please, Sam D Howison, Fumio Arai, Ben D MacArthur
Pluripotent stem cells can self-renew in culture and differentiate along all somatic lineages in vivo. While much is known about the molecular basis of pluripotency, the mechanisms of differentiation remain unclear. Here, we profile individual mouse embryonic stem cells as they progress along the neuronal lineage. We observe that cells pass from the pluripotent state to the neuronal state via an intermediate epiblast-like state. However, analysis of the rate at which cells enter and exit these observed cell states using a hidden Markov model indicates the presence of a chain of unobserved molecular states that each cell transits through stochastically in sequence...
September 27, 2017: Cell Systems
https://www.readbyqxmd.com/read/28928395/stochastic-priming-and-spatial-cues-orchestrate-heterogeneous-clonal-contribution-to-mouse-pancreas-organogenesis
#6
Hjalte List Larsen, Laura Martín-Coll, Alexander Valentin Nielsen, Christopher V E Wright, Ala Trusina, Yung Hae Kim, Anne Grapin-Botton
Spatiotemporal balancing of cellular proliferation and differentiation is crucial for postnatal tissue homoeostasis and organogenesis. During embryonic development, pancreatic progenitors simultaneously proliferate and differentiate into the endocrine, ductal and acinar lineages. Using in vivo clonal analysis in the founder population of the pancreas here we reveal highly heterogeneous contribution of single progenitors to organ formation. While some progenitors are bona fide multipotent and contribute progeny to all major pancreatic cell lineages, we also identify numerous unipotent endocrine and ducto-endocrine bipotent clones...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28855321/the-role-of-stochastic-thermal-environments-in-modulating-the-thermal-physiology-of-an-intertidal-limpet-lottia-digitalis
#7
Madeline J Drake, Nathan A Miller, Anne E Todgham
Much of our understanding of the thermal physiology of intertidal organisms comes from experiments with animals acclimated under constant conditions and exposed to a single heat stress. In nature, however, the thermal environment is more complex. Aerial exposure and the unpredictable nature of thermal stress during low tides may be critical factors in defining the thermal physiology of intertidal organisms. In the fingered limpet, Lottia digitalis, we investigated whether upper temperature tolerance and thermal sensitivity were influenced by the pattern of fluctuation with which thermal stress was applied...
September 1, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28845388/integrated-experimental-and-theoretical-studies-of-stem-cells
#8
REVIEW
Hanna L Sladitschek, Pierre A Neveu
PURPOSE OF REVIEW: Stem cells have to balance self-renewal and differentiation. The dynamic nature of these fate decisions has made stem cell study by traditional methods particularly challenging. Here we highlight recent advances in the field that draw on combining quantitative experiments and modeling to illuminate the biology of stem cells both in vitro and in vivo. RECENT FINDINGS: Recent studies have shown that seemingly complex processes such as the fate decision-making of stem cells or the self-organization of developing tissues obey remarkably simple mathematical models...
2017: Current Stem Cell Reports
https://www.readbyqxmd.com/read/28836397/stochastic-cell-fate-and-longevity-of-offspring
#9
Faezeh Dorri, Hamid Pezeshk, Mehdi Sadeghi
OBJECTIVE: Cellular decision-making is a key process in which cells with similar geneticand environmental background make dissimilar decisions. This stochastic process, which happens in prokaryotic and eukaryotic cells including stem cells, causes cellular diversity and phenotypic variation. In addition, fitness predicts and describes changes in the genetic composition of populations throughout the evolutionary history. Fitness may thus be defined as the ability to adapt and produce surviving offspring...
October 2017: Cell Journal
https://www.readbyqxmd.com/read/28815872/a-multimethod-computational-simulation-approach-for-investigating-mitochondrial-dynamics-and-dysfunction-in-degenerative-aging
#10
Timothy E Hoffman, Katherine J Barnett, Lyle Wallis, William H Hanneman
Research in biogerontology has largely focused on the complex relationship between mitochondrial dysfunction and biological aging. In particular, the mitochondrial free radical theory of aging (MFRTA) has been well accepted. However, this theory has been challenged by recent studies showing minimal increases in reactive oxygen species (ROS) as not entirely deleterious in nature, and even beneficial under the appropriate cellular circumstances. To assess these significant and nonintuitive observations in the context of a functional system, we have taken an in silico approach to expand the focus of the MFRTA by including other key mitochondrial stress response pathways, as they have been observed in the nematode Caenorhabditis elegans...
August 16, 2017: Aging Cell
https://www.readbyqxmd.com/read/28814770/rapid-phenotypic-individualization-of-bacterial-sister-cells
#11
Sander K Govers, Antoine Adam, Hendrik Blockeel, Abram Aertsen
A growing bacterium typically divides into two genetically identical and morphologically similar sister cells and eventually gives rise to a clonal population. Nevertheless, significant phenotypic differentiation among isogenic cells frequently occurs, with the resulting heterogeneity in cellular behavior often ensuring population level growth and survival in complex and unpredictable environments. Although several mechanisms underlying the generation of phenotypic heterogeneity have been elucidated, the speed with which identical sister cells tend to phenotypically diverge from each other has so far remained unaddressed...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28799233/stochastics-of-cellular-differentiation-explained-by-epigenetics-the-case-of-t-cell-differentiation-and-functional-plasticity
#12
REVIEW
J Bhat, J Helmuth, G Chitadze, L Kouakanou, C Peters, M Vingron, O Ammerpohl, D Kabelitz
Epigenetic marks including histone modifications and DNA methylation are associated with 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...
October 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28729483/epigenetic-plasticity-and-the-hallmarks-of-cancer
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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