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Stochasticity of cellular differentiation

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https://www.readbyqxmd.com/read/29709110/making-lineage-decisions-with-biological-noise-lessons-from-the-early-mouse-embryo
#1
REVIEW
Claire S Simon, Anna-Katerina Hadjantonakis, Christian Schröter
Understanding how individual cells make fate decisions that lead to the faithful formation and homeostatic maintenance of tissues is a fundamental goal of contemporary developmental and stem cell biology. Seemingly uniform populations of stem cells and multipotent progenitors display a surprising degree of heterogeneity, primarily originating from the inherent stochastic nature of molecular processes underlying gene expression. Despite this heterogeneity, lineage decisions result in tissues of a defined size and with consistent proportions of differentiated cell types...
April 30, 2018: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/29707543/modeling-based-investigation-of-the-effect-of-noise-in-cellular-systems
#2
REVIEW
Didier Gonze, Claude Gérard, Benjamin Wacquier, Aurore Woller, Alen Tosenberger, Albert Goldbeter, Geneviève Dupont
Noise is pervasive in cellular biology and inevitably affects the dynamics of cellular processes. Biological systems have developed regulatory mechanisms to ensure robustness with respect to noise or to take advantage of stochasticity. We review here, through a couple of selected examples, some insights on possible robustness factors and constructive roles of noise provided by computational modeling. In particular, we focus on (1) factors that likely contribute to the robustness of oscillatory processes such as the circadian clocks and the cell cycle, (2) how reliable coding/decoding of calcium-mediated signaling could be achieved in presence of noise and, in some cases, enhanced through stochastic resonance, and (3) how embryonic cell differentiation processes can exploit stochasticity to create heterogeneity in a population of identical cells...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29660842/kinetic-models-of-hematopoietic-differentiation
#3
REVIEW
Victor Olariu, Carsten Peterson
As cell and molecular biology is becoming increasingly quantitative, there is an upsurge of interest in mechanistic modeling at different levels of resolution. Such models mostly concern kinetics and include gene and protein interactions as well as cell population dynamics. The final goal of these models is to provide experimental predictions, which is now taking on. However, even without matured predictions, kinetic models serve the purpose of compressing a plurality of experimental results into something that can empower the data interpretation, and importantly, suggesting new experiments by turning "knobs" in silico...
April 16, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/29477556/stochastic-cellular-automata-model-of-neurosphere-growth-roles-of-proliferative-potential-contact-inhibition-cell-death-and-phagocytosis
#4
Rifat Sipahi, Günther K H Zupanc
Neural stem and progenitor cells isolated from the central nervous system form, under specific culture conditions, clonal cell clusters known as neurospheres. The neurosphere assay has proven to be a powerful in vitro system to study the behavior of such cells and the development of their progeny. However, the theory of neurosphere growth has remained poorly understood. To overcome this limitation, we have, in the present paper, developed a cellular automata model, with which we examined the effects of proliferative potential, contact inhibition, cell death, and clearance of dead cells on growth rate, final size, and composition of neurospheres...
May 14, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29422612/csde1-binds-transcripts-involved-in-protein-homeostasis-and-controls-their-expression-in-an-erythroid-cell-line
#5
Kat S Moore, Nurcan Yagci, Floris van Alphen, Nahuel A Paolini, Rastislav Horos, Ntsiki M Held, Riekelt H Houtkooper, Emile van den Akker, Alexander B Meijer, Peter A C 't Hoen, Marieke von Lindern
Expression of the RNA-binding protein Csde1 (Cold shock domain protein e1) is strongly upregulated during erythropoiesis compared to other hematopoietic lineages. Csde1 expression is impaired in the severe congenital anemia Diamond Blackfan Anemia (DBA), and reduced expression of Csde1 in healthy erythroblasts impaired their proliferation and differentiation. To investigate the cellular pathways controlled by Csde1 in erythropoiesis, we identified the transcripts that physically associate with Csde1 in erythroid cells...
February 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29340399/landscape-of-gene-networks-for-random-parameter-perturbation
#6
Chunhe Li
Landscape approaches have been exploited to study the stochastic dynamics of gene networks. However, how to calculate the landscape with a wide range of parameter variations and how to investigate the influence of the network topology on the global properties of gene networks remain to be elucidated. Here, I developed an approach for the landscape of random parameter perturbation (LRPP) to address this issue. Based on a self-consistent approximation approach, by making perturbations to parameters in a given range, I obtained the landscape for gene network systems...
February 19, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/29197990/modeling-mechanical-inhomogeneities-in-small-populations-of-proliferating-monolayers-and-spheroids
#7
Emma Lejeune, Christian Linder
Understanding the mechanical behavior of multicellular monolayers and spheroids is fundamental to tissue culture, organism development, and the early stages of tumor growth. Proliferating cells in monolayers and spheroids experience mechanical forces as they grow and divide and local inhomogeneities in the mechanical microenvironment can cause individual cells within the multicellular system to grow and divide at different rates. This differential growth, combined with cell division and reorganization, leads to residual stress...
December 2, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/29186174/parallel-arrangements-of-positive-feedback-loops-limit-cell-to-cell-variability-in-differentiation
#8
Anupam Dey, Debashis Barik
Cellular differentiations are often regulated by bistable switches resulting from specific arrangements of multiple positive feedback loops (PFL) fused to one another. Although bistability generates digital responses at the cellular level, stochasticity in chemical reactions causes population heterogeneity in terms of its differentiated states. We hypothesized that the specific arrangements of PFLs may have evolved to minimize the cellular heterogeneity in differentiation. In order to test this we investigated variability in cellular differentiation controlled either by parallel or serial arrangements of multiple PFLs having similar average properties under extrinsic and intrinsic noises...
2017: PloS One
https://www.readbyqxmd.com/read/29181975/alteration-in-microrna-expression-governs-the-nature-and-timing-of-cellular-fate-commitment
#9
Dola Sengupta, Sandip Kar
In the central nervous system, the expression level of transcriptional repressor Hes1 (hairy and enhancer of split-1) tightly controls the alternative cell fate commitment during differentiation as well as the time required for such cellular transitions. A microRNA, miR-9, that interacts with Hes1 in a mutually antagonistic manner, influences both the process of lineage specification and timing of differentiation significantly, but the impact of the miR-9 in guiding these events still remains poorly understood...
December 13, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29119506/complexity-of-biochemical-and-genetic-responses-reduced-using-simple-theoretical-models
#10
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
#11
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...
November 21, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/29030469/single-cell-gene-expression-analysis-reveals-regulators-of-distinct-cell-subpopulations-among-developing-human-neurons
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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...
December 2017: Aging Cell
https://www.readbyqxmd.com/read/28814770/rapid-phenotypic-individualization-of-bacterial-sister-cells
#20
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
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