scholarly journals Effects of cell cycle variability on lineage and population measurements of mRNA abundance

2020 ◽  
Author(s):  
Ruben Perez-Carrasco ◽  
Casper Beentjes ◽  
Ramon Grima
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Negative Binomial ◽  
Eukaryotic Cell ◽  
Cycle Duration ◽  
Cell Cycle Duration ◽  
Monotonically Decreasing Function ◽  
Binomial Mixture ◽  
A Cell ◽  
The Mean

AbstractMany models of gene expression do not explicitly incorporate a cell cycle description. Here we derive a theory describing how mRNA fluctuations for constitutive and bursty gene expression are influenced by stochasticity in the duration of the cell cycle and the timing of DNA replication. Analytical expressions for the moments show that omitting cell cycle duration introduces an error in the predicted mean number of mRNAs that is a monotonically decreasing function of η, which is proportional to the ratio of the mean cell cycle duration and the mRNA lifetime. By contrast, the error in the variance of the mRNA distribution is highest for intermediate values of η consistent with genome-wide measurements in many organisms. Using eukaryotic cell data, we estimate the errors in the mean and variance to be at most 3% and 25%, respectively. Furthermore, we derive an accurate negative binomial mixture approximation to the mRNA distribution. This indicates that stochasticity in the cell cycle can introduce fluctuations in mRNA numbers that are similar to the effect of bursty transcription. Finally, we show that for real experimental data, disregarding cell cycle stochasticity can introduce errors in the inference of transcription rates larger than 10%.

scholarly journals Effects of cell cycle variability on lineage and population measurements of messenger RNA abundance

2020 ◽  
Vol 17 (168) ◽  
pp. 20200360 ◽  
Author(s):  
Ruben Perez-Carrasco ◽  
Casper Beentjes ◽  
Ramon Grima
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Messenger Rna ◽  
Negative Binomial ◽  
Eukaryotic Cell ◽  
Cycle Duration ◽  
Cell Cycle Duration ◽  
Monotonically Decreasing Function ◽  
Binomial Mixture ◽  
The Mean

Many models of gene expression do not explicitly incorporate a cell cycle description. Here, we derive a theory describing how messenger RNA (mRNA) fluctuations for constitutive and bursty gene expression are influenced by stochasticity in the duration of the cell cycle and the timing of DNA replication. Analytical expressions for the moments show that omitting cell cycle duration introduces an error in the predicted mean number of mRNAs that is a monotonically decreasing function of η , which is proportional to the ratio of the mean cell cycle duration and the mRNA lifetime. By contrast, the error in the variance of the mRNA distribution is highest for intermediate values of η consistent with genome-wide measurements in many organisms. Using eukaryotic cell data, we estimate the errors in the mean and variance to be at most 3% and 25%, respectively. Furthermore, we derive an accurate negative binomial mixture approximation to the mRNA distribution. This indicates that stochasticity in the cell cycle can introduce fluctuations in mRNA numbers that are similar to the effect of bursty transcription. Finally, we show that for real experimental data, disregarding cell cycle stochasticity can introduce errors in the inference of transcription rates larger than 10%.

VIII. Untersuchungen zum Kohlenstoff-Stoffwechsel unbestrahlter Zellen

1966 ◽  
Vol 21 (11) ◽  
pp. 1089-1096 ◽  
Author(s):  
W. Pohlit ◽  
W. Laskowski ◽  
E.-R. Lochmann
Keyword(s):  
Cell Cycle ◽  
Carbon Metabolism ◽  
Quantitative Data ◽  
Diploid Cell ◽  
Cell Multiplication ◽  
Cycle Duration ◽  
Cell Cycle Duration ◽  
Simultaneous Utilization ◽  
A Cell ◽  
Respiratory Deficient

Some quantitative data about the carbon-metabolism in Saccharomyces-cells of different ploidy were determined. The amount of carbon, necessary for the formation of a cell, proved to be proportional to the degree of ploidy of the cells. For the duplication of a diploid cell 6,7·10-11g glucose were used. In comparison with respiratory deficient cells the simultaneous utilization of fermentation and respiration metabolism in respiration sufficient cells leads to a decrease of the cell cycle duration, however, the energy needed for the formation of a cell is not decreased. The rate of cell multiplication has a maximum at about 30 °C for all classes of ploidy. Certain assumptions about the utilization of the carbon source were confirmed by experiments with 14C marked glucose.

scholarly journals Effect of morphactin (chlorfluorenol IT 3456) on the mitotic activity and cell growth in roots of Pisum sativum L.

2014 ◽  
Vol 51 (1) ◽  
pp. 39-50 ◽  
Author(s):  
Barbara Gabara
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Growth ◽  
Thymidine Incorporation ◽  
S Phase ◽  
Cycle Duration ◽  
Nuclear Surface ◽  
Pisum Sativum L ◽  
Cell Cycle Duration ◽  
The Mean

Morphactin in a concentration of 100 ppm does not retard pea root growth, however, it reduced the frequency of cell division and shifted the main wave of mitoses in the 24 h period from 1 to 2 mm of root segment. The mean cell cycle duration is prolonged from 14 h in the control to 22 h in morphactin-treated roots. In the presence of morphactin the decrease of <sup>3</sup>H-thymidine incorporation and diminution of labelling index is accompanied by reduction of the nuclear surface area. The described changes are not accompanied by shortening of cell length. The results obtained suggest that morphactin disturbs the mechanisms regulating the initiation of S phase and its regular course. Moreover, it inhibits the endomitotic replication of DNA.

Genome in toto

Genome ◽  
1999 ◽  
Vol 42 (2) ◽  
pp. 361-362 ◽  
Author(s):  
Alexander E Vinogradov
Keyword(s):  
Cell Cycle ◽  
Genome Evolution ◽  
Genome Size ◽  
Cycle Duration ◽  
Noncoding Dna ◽  
Cell Cycle Duration ◽  
The Relationship

At a certain temperature, which is a compromise for temperatures at which the species are adapted, the relationship between genome size and cell cycle duration during synchronous cleavage divisions can be very strong (r = 1.00, P < 0.01) in four closely related frogs, suggesting a functional dependence.Key words: genome size, genome evolution, genome cytoecology, noncoding DNA, cell cycle duration.

scholarly journals Lateral Root Priming Synergystically Arises from Root Growth and Auxin Transport Dynamics

2018 ◽  
Author(s):  
Thea van den Berg ◽  
Kirsten H. ten Tusscher
Keyword(s):  
Cell Cycle ◽  
Root Growth ◽  
Lateral Root ◽  
Root Formation ◽  
Growth Dynamics ◽  
Root Tip ◽  
Cycle Duration ◽  
Elongation Zone ◽  
Lateral Root Formation ◽  
Cell Cycle Duration

AbstractThe root system is a major determinant of plant fitness. Its capacity to supply the plant with sufficient water and nutrients strongly depends on root system architecture, which arises from the repeated branching off of lateral roots. A critical first step in lateral root formation is priming, which prepatterns sites competent of forming a lateral root. Priming is characterized by temporal oscillations in auxin, auxin signalling and gene expression in the root meristem, which through growth become transformed into a spatially repetitive pattern of competent sites. Previous studies have demonstrated the importance of auxin synthesis, transport and perception for the amplitude of these oscillations and their chances of producing an actual competent site. Additionally, repeated lateral root cap apoptosis was demonstrated to be strongly correlated with repetitive lateral root priming. Intriguingly, no single mutation has been identified that fully abolishes lateral root formation, and thusfar the mechanism underlying oscillations has remained unknown. In this study, we investigated the impact of auxin reflux loop properties combined with root growth dynamics on priming, using a computational approach. To this end we developed a novel multi-scale root model incorporating a realistic root tip architecture and reflux loop properties as well as root growth dynamics. Excitingly, in this model, repetitive auxin elevations automatically emerge. First, we show that root tip architecture and reflux loop properties result in an auxin loading zone at the start of the elongation zone, with preferential auxin loading in narrow vasculature cells. Second, we demonstrate how meristematic root growth dynamics causes regular alternations in the sizes of cells arriving at the elongation zone, which subsequently become amplified during cell expansion. These cell size differences translate into differences in cellular auxin loading potential. Combined, these properties result in temporal and spatial fluctuations in auxin levels in vasculature and pericycle cells. Our model predicts that temporal priming frequency predominantly depends on cell cycle duration, while cell cycle duration together with meristem size control lateral root spacing.

scholarly journals Repurposing of KLF5 activates a cell cycle signature during the progression from a precursor state to oesophageal adenocarcinoma

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Connor Rogerson ◽  
Samuel Ogden ◽  
Edward Britton ◽  
Yeng Ang ◽  
Andrew D Sharrocks ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Prognostic Significance ◽  
Gene Expression Signature ◽  
Chromatin Accessibility ◽  
Oesophageal Adenocarcinoma ◽  
Cell Cycle Gene ◽  
Molecular Events ◽  
Common Causes ◽  
A Cell

Oesophageal adenocarcinoma (OAC) is one of the most common causes of cancer deaths. Barrett’s oesophagus (BO) is the only known precancerous precursor to OAC, but our understanding about the molecular events leading to OAC development is limited. Here, we have integrated gene expression and chromatin accessibility profiles of human biopsies and identified a strong cell cycle gene expression signature in OAC compared to BO. Through analysing associated chromatin accessibility changes, we have implicated the transcription factor KLF5 in the transition from BO to OAC. Importantly, we show that KLF5 expression is unchanged during this transition, but instead, KLF5 is redistributed across chromatin to directly regulate cell cycle genes specifically in OAC cells. This new KLF5 target gene programme has potential prognostic significance as high levels correlate with poorer patient survival. Thus, the repurposing of KLF5 for novel regulatory activity in OAC provides new insights into the mechanisms behind disease progression.

scholarly journals Repurposing of KLF5 activates a cell cycle signature during the progression from a precursor state to Oesophageal Adenocarcinoma

2020 ◽  
Author(s):  
Connor Rogerson ◽  
Samuel Ogden ◽  
Edward Britton ◽  
Yeng Ang ◽  
Andrew D. Sharrocks ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Prognostic Significance ◽  
Gene Expression Signature ◽  
Chromatin Accessibility ◽  
Oesophageal Adenocarcinoma ◽  
Cell Cycle Gene ◽  
A Cell

AbstractOesophageal adenocarcinoma (OAC) is one of the most common causes of cancer deaths and yet compared to other common cancers, we know relatively little about the underlying molecular mechanisms. Barrett’s oesophagus (BO) is the only known precancerous precursor to OAC, but our understanding about the specific events leading to OAC development is limited. Here, we have integrated gene expression and chromatin accessibility profiles of human biopsies of BO and OAC and identified a strong cell cycle gene expression signature in OAC compared to BO. Through analysing associated chromatin accessibility changes, we have implicated the transcription factor KLF5 in the transition from BO to OAC. Importantly, we show that KLF5 expression is unchanged during this transition, but instead, KLF5 is redistributed across chromatin in OAC cells to directly regulate cell cycle genes specifically in OAC. Our findings have potential prognostic significance as the survival of patients with high expression of KLF5 target genes is significantly lower. We have provided new insights into the gene expression networks in OAC and the mechanisms behind progression to OAC, chiefly the repurposing of KLF5 for novel regulatory activity in OAC.

Sign in / Sign up

Export Citation Format

Share Document