scholarly journals Adaptive tuning of cell sensory diversity without changes in gene expression

2020 ◽  
Vol 6 (46) ◽  
pp. eabc1087
Author(s):  
K. Kamino ◽  
J. M. Keegstra ◽  
J. Long ◽  
T. Emonet ◽  
T. S. Shimizu
Keyword(s):  
Gene Expression ◽  
Posttranslational Modifications ◽  
Phenotypic Diversity ◽  
Covalent Modification ◽  
Environmental Cues ◽  
Bet Hedging ◽  
Allosteric Coupling ◽  
The Face ◽  
Survival And Growth ◽  
Cell Variation

In the face of uncertainty, cell populations tend to diversify to enhance survival and growth. Previous studies established that cells can optimize such bet hedging upon environmental change by modulating gene expression to adapt both the average and diversity of phenotypes. Here, we demonstrate that cells can tune phenotypic diversity also using posttranslational modifications. In the chemotaxis network of Escherichia coli, we find, for both major chemoreceptors Tar and Tsr, that cell-to-cell variation in response sensitivity is dynamically modulated depending on the presence or absence of their cognate chemoeffector ligands in the environment. Combining experiments with mathematical modeling, we show that this diversity tuning requires only the environment-dependent covalent modification of chemoreceptors and a standing cell-to-cell variation in their allosteric coupling. Thus, when environmental cues are unavailable, phenotypic diversity enhances the population’s readiness for many signals. However, once a signal is perceived, the population focuses on tracking that signal.

scholarly journals Hsf1 phosphorylation generates cell-to-cell variation in Hsp90 levels and promotes phenotypic plasticity

2017 ◽  
Author(s):  
Xu Zheng ◽  
Ali Beyzavi ◽  
Joanna Krakowiak ◽  
Nikit Patel ◽  
Ahmad S. Khalil ◽  
...  
Keyword(s):  
Gene Expression ◽  
Phenotypic Plasticity ◽  
Important Determinant ◽  
Phenotypic Diversity ◽  
Yeast Cells ◽  
Wide Range ◽  
Differential Tuning ◽  
Gene Expression Heterogeneity ◽  
Noise In Gene Expression ◽  
Cell Variation

ABSTRACTClonal populations of cells exhibit cell-to-cell variation in the transcription of individual genes. In addition to this “noise” in gene expression, heterogeneity in the proteome and the proteostasis network expands the phenotypic diversity of a population. Heat shock transcription factor (Hsf1) regulates chaperone gene expression, thereby coupling transcriptional noise to proteostasis. Here we show that cell-to-cell variation in Hsf1 activity is an important determinant of phenotypic plasticity. Budding yeast cells with high Hsf1 activity were enriched for the ability to acquire resistance to an antifungal drug, and this enrichment depended on Hsp90 – a known “phenotypic capacitor” and canonical Hsf1 target. We show that Hsf1 phosphorylation promotes cell-to-cell variation, and this variation – rather than absolute Hsf1 activity – promotes antifungal resistance. We propose that Hsf1 phosphorylation enables differential tuning of the proteostasis network in individual cells, allowing populations to access a wide range of phenotypic states.

scholarly journals Adaptive noise

2013 ◽  
Vol 280 (1767) ◽  
pp. 20131104 ◽  
Author(s):  
Mark Viney ◽  
Sarah E. Reece
Keyword(s):  
Gene Expression ◽  
Gene Networks ◽  
Phenotypic Diversity ◽  
Biological Systems ◽  
Bet Hedging ◽  
Hedging Strategy ◽  
Phenotypic Differences ◽  
Fitness Benefits ◽  
Adaptive Noise ◽  
Noise In Gene Expression

In biology, noise implies error and disorder and is therefore something which organisms may seek to minimize and mitigate against. We argue that such noise can be adaptive. Recent studies have shown that gene expression can be noisy, noise can be genetically controlled, genes and gene networks vary in how noisy they are and noise generates phenotypic differences among genetically identical cells. Such phenotypic differences can have fitness benefits, suggesting that evolution can shape noise and that noise may be adaptive. For example, gene networks can generate bistable states resulting in phenotypic diversity and switching among individual cells of a genotype, which may be a bet hedging strategy. Here, we review the sources of noise in gene expression, the extent to which noise in biological systems may be adaptive and suggest that applying evolutionary rigour to the study of noise is necessary to fully understand organismal phenotypes.

scholarly journals Nomadic-colonial life strategies enable paradoxical survival and growth despite habitat destruction

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Zong Xuan Tan ◽  
Kang Hao Cheong
Keyword(s):  
Population Model ◽  
Environmental Variability ◽  
Phenotypic Diversity ◽  
Habitat Destruction ◽  
Population Persistence ◽  
Parrondo’S Paradox ◽  
The Face ◽  
Survival And Growth ◽  
Or History

Organisms often exhibit behavioral or phenotypic diversity to improve population fitness in the face of environmental variability. When each behavior or phenotype is individually maladaptive, alternating between these losing strategies can counter-intuitively result in population persistence–an outcome similar to the Parrondo’s paradox. Instead of the capital or history dependence that characterize traditional Parrondo games, most ecological models which exhibit such paradoxical behavior depend on the presence of exogenous environmental variation. Here we present a population model that exhibits Parrondo’s paradox through capital and history-dependent dynamics. Two sub-populations comprise our model: nomads, who live independently without competition or cooperation, and colonists, who engage in competition, cooperation, and long-term habitat destruction. Nomads and colonists may alternate behaviors in response to changes in the colonial habitat. Even when nomadism and colonialism individually lead to extinction, switching between these strategies at the appropriate moments can paradoxically enable both population persistence and long-term growth.

Coral husbandry for ocean futures: leveraging abiotic factors to increase survivorship, growth, and resilience in juvenile Montipora capitata

2021 ◽  
Vol 657 ◽  
pp. 123-133
Author(s):  
JR Hancock ◽  
AR Barrows ◽  
TC Roome ◽  
AS Huffmyer ◽  
SB Matsuda ◽  
...  
Keyword(s):  
Abiotic Factors ◽  
Larval Rearing ◽  
Abiotic Conditions ◽  
Montipora Capitata ◽  
Reef Restoration ◽  
Juvenile Corals ◽  
Bleaching Response ◽  
The Face ◽  
Survival And Growth ◽  
Global And Local

Reef restoration via direct outplanting of sexually propagated juvenile corals is a key strategy in preserving coral reef ecosystem function in the face of global and local stressors (e.g. ocean warming). To advance our capacity to scale and maximize the efficiency of restoration initiatives, we examined how abiotic conditions (i.e. larval rearing temperature, substrate condition, light intensity, and flow rate) interact to enhance post-settlement survival and growth of sexually propagated juvenile Montipora capitata. Larvae were reared at 3 temperatures (high: 28.9°C, ambient: 27.2°C, low: 24.5°C) for 72 h during larval development, and were subsequently settled on aragonite plugs conditioned in seawater (1 or 10 wk) and raised in different light and flow regimes. These juvenile corals underwent a natural bleaching event in Kāne‘ohe Bay, O‘ahu, Hawai‘i (USA), in summer 2019, allowing us to opportunistically measure bleaching response in addition to survivorship and growth. This study demonstrates how leveraging light and flow can increase the survivorship and growth of juvenile M. capitata. In contrast, larval preconditioning and substrate conditioning had little overall effect on survivorship, growth, or bleaching response. Importantly, there was no optimal combination of abiotic conditions that maximized survival and growth in addition to bleaching tolerances. This study highlights the ability to tailor sexual reproduction for specific restoration goals by addressing knowledge gaps and incorporating practices that could improve resilience in propagated stocks.

A Single-Center Trial to Evaluate the Efficacy and Tolerability of Four Microneedling Treatments on Fine Lines and Wrinkles of Facial and Neck Skin in Subjects With Fitzpatrick Skin Types I-IV: An Objective Assessment Using Non-Invasive Devices and 0.33mm Microbiopsies

2021 ◽  
Author(s):  
Christine E Wamsley ◽  
Mikaela Kislevitz ◽  
Jennifer Barillas ◽  
Deniz Basci ◽  
Vishal Kandagatla ◽  
...  
Keyword(s):  
Gene Expression ◽  
Objective Assessment ◽  
Standard Of Care ◽  
Transepidermal Water Loss ◽  
Post Treatment ◽  
Non Invasive ◽  
Muscle Formation ◽  
The Face ◽  
High Resolution Ultrasonography ◽  
Elastin Gene

Abstract Background While ablative techniques have been standard of care for the treatment of fine lines and wrinkles, microneedling is a minimally invasive alternative. Objectives The purpose of this study was to assess the efficacy of microneedling on facial and neck fine lines and wrinkles. Methods 35 subjects between 44 and 65 years old with Fitzpatrick skin types I-IV received four monthly microneedling treatments over the face and neck. Subjects returned one and three months post-treatment. At every visit, high-resolution ultrasonography, optical coherence tomography, transepidermal water loss and BTC-2000 were performed. 0.33mm microbiopsies were collected pre-treatment, before the fourth treatment and three months post-treatment. Results 32 subjects (93.75% female, 6.25% male) completed all seven visits. Facial dermal and epidermal density increased 101.86% and 19.28%, respectively from baseline at three months post-treatment. Facial elasticity increased 28.2% from baseline three months post-treatment. Facial attenuation coefficient increased 15.65% and 17.33% one and three months post-treatment. At study completion, blood flow 300µm deep decreased 25.8% in the face and 42.3% in the neck. Relative collagen type III and elastin gene expression was statistically higher three months post-treatment. However, total elastin protein levels unchanged compared to baseline. 58% of biopsies extracted three months post-treatment showed dermal muscle formation, compared to baseline 15.3%. Conclusions The results illustrate the effects of microneedling treatments. Non-invasive measurements and biopsy data showed changes in skin architecture and collagen/elastin gene expression suggesting skin rejuvenation, with new extracellular matrix production and muscle formation.

scholarly journals Combinatorial Control of Gene Expression

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Soumya Bhattacharjee ◽  
Kaushik Renganaath ◽  
Rajesh Mehrotra ◽  
Sandhya Mehrotra
Keyword(s):  
Gene Expression ◽  
Short Description ◽  
Controlling Factors ◽  
Environmental Cues ◽  
Control Of Gene Expression ◽  
Environmental Signals ◽  
Combinatorial Control ◽  
Sense And Respond ◽  
Eukaryotic Organisms

The complexity and diversity of eukaryotic organisms are a feat of nature’s engineering. Pulling the strings of such an intricate machinery requires an even more masterful and crafty approach. Only the number and type of responses that they generate exceed the staggering proportions of environmental signals perceived and processed by eukaryotes. Hence, at first glance, the cell’s sparse stockpile of controlling factors does not seem remotely adequate to carry out this response. The question as to how eukaryotes sense and respond to environmental cues has no single answer. It is an amalgamation, an interplay between several processes, pathways, and factors—a combinatorial control. A short description of some of the most important elements that operate this entire conglomerate is given in this paper.

scholarly journals Evolutionary Analysis of Transcriptional Regulation Mediated by Cdx2 in Rodents

2021 ◽  
Author(s):  
Weizheng Liang ◽  
Guipeng Li ◽  
Huanhuan Cui ◽  
Yukai Wang ◽  
Wencheng Wei ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Amino Acid ◽  
Dna Binding ◽  
Phenotypic Diversity ◽  
Embryonic Stem ◽  
Regulatory Elements ◽  
Evolutionary Analysis ◽  
Protein Sequence Analysis ◽  
Systematic Analysis

AbstractDifferences in gene expression, which can arise from divergence in cis-regulatory elements or alterations in transcription factors binding specificity, are one of the most important causes of phenotypic diversity during evolution. By protein sequence analysis, we observed high sequence conservation in the DNA binding domain (DBD) of the transcription factor Cdx2 across many vertebrates, whereas three amino acid changes were exclusively found in mouse Cdx2 (mCdx2), suggesting potential positive selection in the mouse lineage. Multi-omics analyses were then carried out to investigate the effects of these changes. Surprisingly, there were no significant functional differences between mCdx2 and its rat homologue (rCdx2), and none of the three amino acid changes had any impact on its function. Finally, we used rat-mouse allodiploid embryonic stem cells (RMES) to study the cis effects of Cdx2-mediated gene regulation between the two rodents. Interestingly, whereas Cdx2 binding is largely divergent between mouse and rat, the transcriptional effect induced by Cdx2 is conserved to a much larger extent.Author summaryOur study 1) represented a first systematic analysis of species-specific adaptation in DNA binding pattern of transcription factor. Although the mouse-specific amino acid changes did not manifest functional impact in our system, several explanations may account for it (See Discussion part for the detail); 2) represented a first study of cis-regulation between two reproductively isolated species by using a novel allodiploid system; 3) demonstrated a higher conservation of transcriptional output than that of DNA binding, suggesting the evolvability/plasticity of the latter; 4) finally provided a rich data resource for Cdx2 mediated regulation, including gene expression, chromatin accessibility and DNA binding etc.

scholarly journals Gene body methylation mediates epigenetic inheritance of plant traits

2021 ◽  
Author(s):  
Zaigham Shahzad ◽  
Jonathan D. Moore ◽  
Daniel Zilberman
Keyword(s):  
Gene Expression ◽  
Flowering Time ◽  
Cytosine Methylation ◽  
Plant Traits ◽  
Phenotypic Diversity ◽  
Strong Association ◽  
Epigenetic Inheritance ◽  
Evolutionary Significance ◽  
Gene Body ◽  
Gene Body Methylation

AbstractCytosine methylation is an epigenetically heritable DNA modification common in plant and animal genes, but the functional and evolutionary significance of gene body methylation (gbM) has remained enigmatic. Here we show that gbM enhances gene expression in Arabidopsis thaliana. We also demonstrate that natural gbM variation influences drought and heat tolerance and flowering time by modulating gene expression, including that of Flowering Locus C (FLC). Notably, epigenetic variation accounts for as much trait heritability in natural populations as DNA sequence polymorphism. Furthermore, we identify gbM variation in numerous genes associated with environmental variables, including a strong association between flowering time, spring atmospheric NO2 – a by-product of fossil fuel burning – and FLC epialleles. Our study demonstrates that gbM is an important modulator of gene expression, and its natural variation fundamentally shapes phenotypic diversity in plant populations. Thus, gbM provides an epigenetic basis for adaptive evolution independent of genetic polymorphism.

scholarly journals Evolution Of Acute Myelogenous Leukemia Stem Cell Properties Following Treatment and Progression

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 883-883 ◽  
Author(s):  
TzuChieh Ho ◽  
Mark W LaMere ◽  
Kristen O'Dwyer ◽  
Jason H. Mendler ◽  
Jane L. Liesveld ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Acute Myelogenous Leukemia ◽  
Cell Model ◽  
Phenotypic Diversity ◽  
Hierarchical Organization ◽  
Myelogenous Leukemia ◽  
Leukemic Cells ◽  
Leukemia Stem Cell ◽  
Acute Myelogenous

Abstract Acute Myelogenous Leukemia (AML) is a disease that clinically evolves over time as many patients who are responsive to therapy upfront acquire resistance to the same agents when applied in the relapse setting. The stem cell model for AML has been invoked to explain primary resistance to standard therapy; the leukemia stem cell (LSC) population representing a therapy-refractory reservoir for relapse. There have been no prospective efforts to formally assess the evolution of the LSC population during patients’ clinical course. We performed a prospective characterization of specimens from a well-defined cohort of patients with AML at diagnosis and relapse to assess the frequency and phenotype of functionally defined LSCs. Methods Primary bone marrow and peripheral blood samples were collected on IRB approved protocols from patients with newly diagnosed AML undergoing induction therapy. Twenty-five patients who relapsed after achieving a complete remission were selected for further study. Screening studies identified seven patients whose pre-therapy samples demonstrated sustained engraftment of NSG mice following transplantation. Pre-therapy and post-relapse LSC frequencies were assessed using xenotransplantation limiting dilution analyses (LDA). We assessed the frequencies of CD45RA, CD32, TIM-3, CD96, CD47, and CD97 expressing populations that have been previously published to possess LSC activity. Functionally validated pre-therapy and post-relapse LSC populations were identified using fluorescent labeled cell sorting and NSG xenotransplantation. LSC activity was confirmed for each population using secondary xenotransplantation. Gene expression analysis of highly enriched LSC populations from pre-therapy and post-relapse samples was performed using ABI TILDA qPCR analyses following pre-amplification. Results We demonstrated by LDA an 8 to 42-fold increase in LSC frequency between diagnosis and relapse in paired primary patient samples. The increase in LSC activity was not associated with an increase in frequency for phenotypically-defined populations previously reported to possess LSC activity. Rather, we found that LSC activity expanded at relapse to immunophenotypic populations of leukemic cells that did not possess LSC activity prior to treatment. Moreover, in all patients, the number of phenotypically distinct LSC populations (as defined by CD34 and CD38 or CD32 and CD38) detectable at relapse was dramatically expanded. Further, while the majority of the LSC populations’ gene expression profile remained stable between diagnosis and relapse, a subset of genes were enriched in defined LSC populations at relapse including IL3-receptor alpha and IL1-RAP, both previously demonstrated to play a role in LSC biology. Conclusions This study is the first to characterize the natural evolution of LSCs in vivo following treatment and relapse. We demonstrate an increase in LSC activity and greatly increased phenotypic diversity of the LSC population, suggesting a loss of hierarchical organization following relapse. These findings demonstrate that treatment of AML patients with conventional chemotherapy regimens can promote quantitative and qualitative expansion of the LSC compartment. Further, the data indicate that surface antigen immune-phenotype is not predictive of function in relapse and suggest a major limitation to efforts targeting specific surface antigens in the relapse setting. Understanding the mechanisms by which LSC expansion occurs and how to target it will likely improve our currently poor treatment options for patients who relapse. Disclosures: Becker: Millenium: Research Funding.

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