Interplay of microRNAs, transcription factors and target genes: linking dynamic expression changes to function

Nucleic Acids Research, Journal Year: 2013, Volume and Issue: 41(5), P. 2817 - 2831

Published: Jan. 17, 2013

MicroRNAs (miRNAs) are ubiquitously expressed small non-coding RNAs that, in most cases, negatively regulate gene expression at the post-transcriptional level. miRNAs involved fine-tuning fundamental cellular processes such as proliferation, cell death and cycle control believed to confer robustness biological responses. Here, we investigated simultaneously transcriptional changes of miRNA mRNA levels over time after activation Janus kinase/Signal transducer activator transcription (Jak/STAT) pathway by interferon-γ stimulation melanoma cells. To examine global patterns, time-series microarray data were analysed. We observed delayed responses (after 24–48 h) with respect mRNAs (12–24 identified functions each step response. Inference upstream regulators allowed for identification reactions stimulation. Linking profiles their annotated functions, demonstrate dynamic interplay functions. Finally, our revealed network motifs form feed-forward loops involving regulators, miRNAs. Additional information obtained from integrating may represent an important towards understanding regulatory principles expression.

Language: Английский

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Considerations for the use of transcriptomics in identifying the ‘genes that matter’ for environmental adaptation

Journal of Experimental Biology, Journal Year: 2015, Volume and Issue: 218(12), P. 1925 - 1935

Published: June 1, 2015

ABSTRACT Transcriptomics has emerged as a powerful approach for exploring physiological responses to the environment. However, like any other experimental approach, transcriptomics its limitations. been criticized an inappropriate method identify genes with large impacts on adaptive environment because: (1) fitness are rare; (2) change in gene expression does not necessarily equate effect fitness; and (3) protein activity is most relevant fitness, mRNA abundance unreliable indicator of activity. In this review, these criticisms re-evaluated context recent systems-level experiments that provide new insight into relationship between during environmental stress. general, remain valid today, indicate exclusively using screen underlie adaptation will overlook constitutively expressed regulatory play major roles setting tolerance limits. Standard practices transcriptomic data analysis pipelines may also be limiting by prioritizing highly differentially conserved over those undergo moderate fold-changes cannot annotated. While certainly do undermine continued widespread use within physiology, they highlight types research questions which best suited need more functional analyses. Such information pertinent at time when become increasingly tractable many researchers contemplating integrating their programs.

Language: Английский

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Predictive biology: modelling, understanding and harnessing microbial complexity

Nature Reviews Microbiology, Journal Year: 2020, Volume and Issue: 18(9), P. 507 - 520

Published: May 29, 2020

Language: Английский

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Biological regulation: controlling the system from within

Biology & Philosophy, Journal Year: 2015, Volume and Issue: 31(2), P. 237 - 265

Published: Aug. 5, 2015

Language: Английский

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A mechanism for epithelial-mesenchymal heterogeneity in a population of cancer cells

PLoS Computational Biology, Journal Year: 2020, Volume and Issue: 16(2), P. e1007619 - e1007619

Published: Feb. 10, 2020

Epithelial-mesenchymal heterogeneity implies that cells within the same tumor can exhibit different phenotypes—epithelial, mesenchymal, or one more hybrid epithelial-mesenchymal phenotypes. This behavior has been reported across cancer types, both in vitro and vivo, implicated multiple processes associated with metastatic aggressiveness including immune evasion, collective dissemination of cells, emergence cell subpopulations stem cell-like properties. However, ability a population to generate, maintain, propagate this remained mystifying feature. Here, we used computational modeling approach show emerge from noise partitioning biomolecules (such as RNAs proteins) among daughter during division cell. Our model captures experimentally observed temporal changes fractions phenotypes murine prostate describes hysteresis population-level dynamics plasticity. The is further able predict how factors known promote phenotype alter phenotypic composition population. Finally, probe implications plasticity for therapeutic regimens found co-targeting epithelial mesenchymal likely be most effective strategy restricting growth. By connecting an intracellular circuit population, our study serves first step towards understanding generation maintenance non-genetic targeting populations.

Language: Английский

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Dynamic stem cell heterogeneity

Development, Journal Year: 2015, Volume and Issue: 142(8), P. 1396 - 1406

Published: April 7, 2015

Recent lineage-tracing studies based on inducible genetic labelling have emphasized a crucial role for stochasticity in the maintenance and regeneration of cycling adult tissues. These revealed that stem cells are frequently lost through differentiation this is compensated by duplication neighbours, leading to consolidation clonal diversity. Through combination long-term assays with short-term vivo live imaging, cellular basis stochastic cell loss replacement has begun be resolved. With focus mammalian spermatogenesis, intestinal hair cycle, we review dynamic heterogeneity regulation populations.

Language: Английский

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Single-Cell and Single-Molecule Analysis of Gene Expression Regulation

Annual Review of Genetics, Journal Year: 2016, Volume and Issue: 50(1), P. 267 - 291

Published: Nov. 23, 2016

Recent advancements in single-cell and single-molecule imaging technologies have resolved biological processes time space that are fundamental to understanding the regulation of gene expression. Observations events their cellular context revealed highly dynamic aspects transcriptional post-transcriptional control eukaryotic cells. This approach can relate transcription with mRNA abundance lifetimes. Another key aspect analysis is cell-to-cell variability among populations Definition heterogeneity has stochastic processes, determined characteristics under-represented cell types or transitional states, integrated behaviors multicellular organisms. In this review, we discuss novel expression cells organisms by latest advances technology.

Language: Английский

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Genome-wide kinetic properties of transcriptional bursting in mouse embryonic stem cells

Science Advances, Journal Year: 2020, Volume and Issue: 6(25)

Published: June 17, 2020

Transcriptional bursting is the stochastic activation and inactivation of promoters, contributing to cell-to-cell heterogeneity in gene expression. However, mechanism underlying regulation transcriptional kinetics (burst size frequency) mammalian cells remains elusive. In this study, we performed single-cell RNA sequencing analyze intrinsic noise mRNA levels for elucidating mouse embryonic stem cells. Informatics analyses functional assays revealed that was regulated by a combination promoter- body-binding proteins, including polycomb repressive complex 2 transcription elongation factors. Furthermore, large-scale CRISPR-Cas9-based screening identified Akt/MAPK signaling pathway modulating efficiency. These results uncovered key molecular mechanisms expression

Language: Английский

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Single-nucleus RNA-seq2 reveals functional crosstalk between liver zonation and ploidy

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: July 12, 2021

Abstract Single-cell RNA-seq reveals the role of pathogenic cell populations in development and progression chronic diseases. In order to expand our knowledge on cellular heterogeneity, we have developed a single-nucleus RNA-seq2 method tailored for comprehensive analysis nuclear transcriptome from frozen tissues, allowing dissection all types present liver, regardless size or fragility. We use this approach characterize transcriptional profile individual hepatocytes with different levels ploidy, discovered that ploidy states are associated metabolic potential, gene expression tetraploid mononucleated is conditioned by their position within hepatic lobule. Our work remarkable crosstalk between dosage spatial distribution hepatocytes.

Language: Английский

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Precision of tissue patterning is controlled by dynamical properties of gene regulatory networks

Development, Journal Year: 2021, Volume and Issue: 148(4)

Published: Feb. 5, 2021

ABSTRACT During development, gene regulatory networks allocate cell fates by partitioning tissues into spatially organised domains of expression. How the sharp boundaries that delineate these expression patterns arise, despite stochasticity associated with regulation, is poorly understood. We show, in vertebrate neural tube, using perturbations coding and regions, structure network contributes to boundary precision. This achieved, not reducing noise individual genes, but configuration modulating ability stochastic fluctuations initiate changes. use a computational screen identify properties influence precision, revealing two dynamical mechanisms which small circuits attenuate effect order increase patterning These results highlight design principles produce precise

Language: Английский

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