scholarly journals The Impact of Epigenetic Signatures on Amniotic Fluid Stem Cell Fate

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Daniela Di Tizio ◽  
Alessandra Di Serafino ◽  
Prabin Upadhyaya ◽  
Luca Sorino ◽  
Liborio Stuppia ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Amniotic Fluid ◽  
Cell Fate ◽  
Histone Modifications ◽  
Current Evidence ◽  
Cell Fate Decisions ◽  
Small Noncoding Rnas ◽  
Tight Correlation ◽  
The Impact

Epigenetic modifications play a significant role in determining the fate of stem cells and in directing the differentiation into multiple lineages. Current evidence indicates that mechanisms involved in chromatin regulation are essential for maintaining stable cell identities. There is a tight correlation among DNA methylation, histone modifications, and small noncoding RNAs during the epigenetic control of stem cells’ differentiation; however, to date, the precise mechanism is still not clear. In this context, amniotic fluid stem cells (AFSCs) represent an interesting model due to their unique features and the possible advantages of their use in regenerative medicine. Recent studies have elucidated epigenetic profiles involved in AFSCs’ lineage commitment and differentiation. In order to use these cells effectively for therapeutic purposes, it is necessary to understand the basis of multiple-lineage potential and elaborate in detail how cell fate decisions are made and memorized. The present review summarizes the most recent findings on epigenetic mechanisms of AFSCs with a focus on DNA methylation, histone modifications, and microRNAs (miRNAs) and addresses how their unique signatures contribute to lineage-specific differentiation.

scholarly journals Quantifying the Stability of Coupled Genetic and Epigenetic Switches With Variational Methods

2021 ◽  
Vol 11 ◽  
Author(s):  
Amogh Sood ◽  
Bin Zhang
Keyword(s):  
Gene Regulation ◽  
Transcription Factors ◽  
Cell Fate ◽  
Histone Modifications ◽  
Regulatory Networks ◽  
Variational Principles ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Fate Decisions ◽  
The Impact

The Waddington landscape provides an intuitive metaphor to view development as a ball rolling down the hill, with distinct phenotypes as basins and differentiation pathways as valleys. Since, at a molecular level, cell differentiation arises from interactions among the genes, a mathematical definition for the Waddington landscape can, in principle, be obtained by studying the gene regulatory networks. For eukaryotes, gene regulation is inextricably and intimately linked to histone modifications. However, the impact of such modifications on both landscape topography and stability of attractor states is not fully understood. In this work, we introduced a minimal kinetic model for gene regulation that combines the impact of both histone modifications and transcription factors. We further developed an approximation scheme based on variational principles to solve the corresponding master equation in a second quantized framework. By analyzing the steady-state solutions at various parameter regimes, we found that histone modification kinetics can significantly alter the behavior of a genetic network, resulting in qualitative changes in gene expression profiles. The emerging epigenetic landscape captures the delicate interplay between transcription factors and histone modifications in driving cell-fate decisions.

scholarly journals Loss of Apc Rapidly Impairs DNA Methylation Programs and Cell Fate Decisions in Lgr5+ Intestinal Stem Cells

2020 ◽  
Vol 80 (11) ◽  
pp. 2101-2113 ◽  
Author(s):  
Marco Bruschi ◽  
Laure Garnier ◽  
Elouan Cleroux ◽  
Alicia Giordano ◽  
Michael Dumas ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Cell Fate ◽  
Intestinal Stem Cells ◽  
Cell Fate Decisions

scholarly journals Bdh2 Deficiency Promotes Endoderm-Biased Early Differentiation of Mouse Embryonic Stem Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuting Fu ◽  
Fangyuan Liu ◽  
Shuo Cao ◽  
Jia Zhang ◽  
Huizhi Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Fate ◽  
Iron Homeostasis ◽  
Embryonic Stem ◽  
Cell Fate Decisions ◽  
Rate Limiting Step ◽  
Fate Decision

3-hydroxybutyrate dehydrogenase-2 (Bdh2), a short-chain dehydrogenase, catalyzes a rate-limiting step in the biogenesis of the mammalian siderophore, playing a key role in iron homeostasis, energy metabolism and apoptosis. However, the function of Bdh2 in embryonic stem cells (ESCs) remains unknown. To gain insights into the role of Bdh2 on pluripotency and cell fate decisions of mouse ESCs, we generated Bdh2 homozygous knockout lines for both mouse advanced embryonic stem cell (ASC) and ESC using CRISPR/Cas9 genome editing technology. Bdh2 deficiency in both ASCs and ESCs had no effect on expression of core pluripotent transcription factors and alkaline phosphatase activity, suggesting dispensability of Bdh2 for self-renewal and pluripotency of ESCs. Interestingly, cells with Bdh2 deficiency exhibited potency of endoderm differentiation in vitro; with upregulated endoderm associated genes revealed by RNA-seq and RT-qPCR. We further demonstrate that Bdh2 loss inhibited expression of multiple methyltransferases (DNMTs) at both RNA and protein level, suggesting that Bdh2 may be essentially required to maintain DNA methylation in ASCs and ESCs. Overall, this study provides valuable data and resources for understanding how Bdh2 regulate earliest cell fate decision and DNA methylation in ASCs/ESCs.

scholarly journals Regulated Fluctuations in Nanog Expression Mediate Cell Fate Decisions in Embryonic Stem Cells

PLoS Biology ◽  
2009 ◽  
Vol 7 (7) ◽  
pp. e1000149 ◽  
Author(s):  
Tibor Kalmar ◽  
Chea Lim ◽  
Penelope Hayward ◽  
Silvia Muñoz-Descalzo ◽  
Jennifer Nichols ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Fate ◽  
Embryonic Stem ◽  
Cell Fate Decisions ◽  
Nanog Expression ◽  
Mediate Cell

scholarly journals Gut Microbiota as Important Mediator Between Diet and DNA Methylation and Histone Modifications in the Host

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 597 ◽  
Author(s):  
Patrizia D’Aquila ◽  
Laurie Lynn Carelli ◽  
Francesco De Rango ◽  
Giuseppe Passarino ◽  
Dina Bellizzi
Keyword(s):  
Dna Methylation ◽  
Gut Microbiota ◽  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Current Evidence ◽  
Long Term Effects ◽  
Metabolic Functions ◽  
Complex Ecosystem ◽  
Short And Long Term ◽  
And Function

The human gut microbiota is a complex ecosystem consisting of trillions of microorganisms that inhabit symbiotically on and in the human intestine. They carry out, through the production of a series of metabolites, many important metabolic functions that complement the activity of mammalian enzymes and play an essential role in host digestion. Interindividual variability of microbiota structure, and consequently of the expression of its genes (microbiome), was largely ascribed to the nutritional regime. Diet influences microbiota composition and function with short- and long-term effects. In spite of the vast literature, molecular mechanisms underlying these effects still remain elusive. In this review, we summarized the current evidence on the role exerted by gut microbiota and, more specifically, by its metabolites in the establishment of the host epigenome. The interest in this topic stems from the fact that, by modulating DNA methylation and histone modifications, the gut microbiota does affect the cell activities of the hosting organism.

scholarly journals Theoretical study of the impact of adaptation on cell-fate heterogeneity and fractional killing

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Julien Hurbain ◽  
Darka Labavić ◽  
Quentin Thommen ◽  
Benjamin Pfeuty
Keyword(s):  
Cell Fate ◽  
Stochastic Dynamics ◽  
Biochemical Networks ◽  
Stochastic Bifurcation ◽  
Modeling Framework ◽  
Life And Death ◽  
Cell Fate Decisions ◽  
Wide Range ◽  
Adaptation Response ◽  
The Impact

Abstract Fractional killing illustrates the cell propensity to display a heterogeneous fate response over a wide range of stimuli. The interplay between the nonlinear and stochastic dynamics of biochemical networks plays a fundamental role in shaping this probabilistic response and in reconciling requirements for heterogeneity and controllability of cell-fate decisions. The stress-induced fate choice between life and death depends on an early adaptation response which may contribute to fractional killing by amplifying small differences between cells. To test this hypothesis, we consider a stochastic modeling framework suited for comprehensive sensitivity analysis of dose response curve through the computation of a fractionality index. Combining bifurcation analysis and Langevin simulation, we show that adaptation dynamics enhances noise-induced cell-fate heterogeneity by shifting from a saddle-node to a saddle-collision transition scenario. The generality of this result is further assessed by a computational analysis of a detailed regulatory network model of apoptosis initiation and by a theoretical analysis of stochastic bifurcation mechanisms. Overall, the present study identifies a cooperative interplay between stochastic, adaptation and decision intracellular processes that could promote cell-fate heterogeneity in many contexts.

scholarly journals A systematic study of critical miRNAs on cells proliferation and apoptosis by the shortest path

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Peng Xu ◽  
Qian Wu ◽  
Deyang Lu ◽  
Jian Yu ◽  
Yongsheng Rao ◽  
...  
Keyword(s):  
Cell Fate ◽  
Shortest Path ◽  
Function Analysis ◽  
Mirna Gene ◽  
Small Noncoding Rnas ◽  
Liver Cancers ◽  
Proliferation And Apoptosis ◽  
Function Modules ◽  
Multiple Cell ◽  
The Impact

Abstract Background MicroRNAs are a class of important small noncoding RNAs, which have been reported to be involved in the processes of tumorigenesis and development by targeting a few genes. Existing studies show that the imbalance between cell proliferation and apoptosis is closely related to the initiation and development of cancers. However, the impact of miRNAs on this imbalance has not been studied systematically. Results In this study, we first construct a cell fate miRNA-gene regulatory network. Then, we propose a systematical method for calculating the global impact of miRNAs on cell fate genes based on the shortest path. Results on breast cancer and liver cancer datasets show that most of the cell fate genes are perturbed by the differentially expressed miRNAs. Most of the top-identified miRNAs are verified in the Human MicroRNA Disease Database (HMDD) and are related to breast and liver cancers. Function analysis shows that the top 20 miRNAs regulate multiple cell fate related function modules and interact tightly based on their functional similarity. Furthermore, more than half of them can promote sensitivity or induce resistance to some anti-cancer drugs. Besides, survival analysis demonstrates that the top-ranked miRNAs are significantly related to the overall survival time in the breast and liver cancers group. Conclusion In sum, this study can help to systematically study the important role of miRNAs on proliferation and apoptosis and thereby uncover the key miRNAs during the process of tumorigenesis. Furthermore, the results of this study will contribute to the development of clinical therapy based miRNAs for cancers.

scholarly journals Do Neural Stem Cells Have a Choice? Heterogenic Outcome of Cell Fate Acquisition in Different Injury Models

2019 ◽  
Vol 20 (2) ◽  
pp. 455 ◽  
Author(s):  
Felix Beyer ◽  
Iria Samper Agrelo ◽  
Patrick Küry
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Ex Vivo ◽  
Meta Analysis ◽  
Cell Types ◽  
Adult Brain ◽  
Repair Capacity ◽  
Cell Fate Decisions ◽  
Limiting Parameters

The adult mammalian central nervous system (CNS) is generally considered as repair restricted organ with limited capacities to regenerate lost cells and to successfully integrate them into damaged nerve tracts. Despite the presence of endogenous immature cell types that can be activated upon injury or in disease cell replacement generally remains insufficient, undirected, or lost cell types are not properly generated. This limitation also accounts for the myelin repair capacity that still constitutes the default regenerative activity at least in inflammatory demyelinating conditions. Ever since the discovery of endogenous neural stem cells (NSCs) residing within specific niches of the adult brain, as well as the description of procedures to either isolate and propagate or artificially induce NSCs from various origins ex vivo, the field has been rejuvenated. Various sources of NSCs have been investigated and applied in current neuropathological paradigms aiming at the replacement of lost cells and the restoration of functionality based on successful integration. Whereas directing and supporting stem cells residing in brain niches constitutes one possible approach many investigations addressed their potential upon transplantation. Given the heterogeneity of these studies related to the nature of grafted cells, the local CNS environment, and applied implantation procedures we here set out to review and compare their applied protocols in order to evaluate rate-limiting parameters. Based on our compilation, we conclude that in healthy CNS tissue region specific cues dominate cell fate decisions. However, although increasing evidence points to the capacity of transplanted NSCs to reflect the regenerative need of an injury environment, a still heterogenic picture emerges when analyzing transplantation outcomes in injury or disease models. These are likely due to methodological differences despite preserved injury environments. Based on this meta-analysis, we suggest future NSC transplantation experiments to be conducted in a more comparable way to previous studies and that subsequent analyses must emphasize regional heterogeneity such as accounting for differences in gray versus white matter.

scholarly journals Runx1 downregulates stem cell and megakaryocytic transcription programs that support niche interactions

Blood ◽  
2016 ◽  
Vol 127 (26) ◽  
pp. 3369-3381 ◽  
Author(s):  
Kira Behrens ◽  
Ioanna Triviai ◽  
Maike Schwieger ◽  
Nilgün Tekin ◽  
Malik Alawi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Cell Adhesion ◽  
Cell Fate ◽  
Bone Marrow Niche ◽  
Cell Fate Decisions ◽  
Multipotent Progenitors ◽  
Key Points

Key Points Runx1 is a key determinant of megakaryocyte cell-fate decisions in multipotent progenitors. Runx1 downregulates cell-adhesion factors that promote residency of stem cells and megakaryocytes in their bone marrow niche.

Sign in / Sign up

Export Citation Format

Share Document