Cell size has gene expression and biophysical consequences for cellular function

2019 ◽  
Vol 6 (1-2) ◽  
pp. 81-94 ◽  
Author(s):  
John A. Raven ◽  
Charles A. Knight ◽  
John Beardall
PLoS ONE ◽  
2020 ◽  
Vol 15 (3) ◽  
pp. e0229468 ◽  
Author(s):  
Iris L. E. van de Pol ◽  
Gert Flik ◽  
Wilco C. E. P. Verberk

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Charlotte N. Miller ◽  
Jack Dumenil ◽  
Fu Hao Lu ◽  
Caroline Smith ◽  
Neil McKenzie ◽  
...  

Abstract Background The same species of plant can exhibit very diverse sizes and shapes of organs that are genetically determined. Characterising genetic variation underlying this morphological diversity is an important objective in evolutionary studies and it also helps identify the functions of genes influencing plant growth and development. Extensive screens of mutagenised Arabidopsis populations have identified multiple genes and mechanisms affecting organ size and shape, but relatively few studies have exploited the rich diversity of natural populations to identify genes involved in growth control. Results We screened a relatively well characterised collection of Arabidopsis thaliana accessions for variation in petal size. Association analyses identified sequence and gene expression variation on chromosome 4 that made a substantial contribution to differences in petal area. Variation in the expression of a previously uncharacterised gene At4g16850 (named as KSK) had a substantial role on variation in organ size by influencing cell size. Over-expression of KSK led to larger petals with larger cells and promoted the formation of stamenoid features. The expression of auxin-responsive genes known to limit cell growth was reduced in response to KSK over-expression. ANT expression was also reduced in KSK over-expression lines, consistent with altered floral identities. Auxin responses were reduced in KSK over-expressing cells, consistent with changes in auxin-responsive gene expression. KSK may therefore influence auxin responses during petal development. Conclusions Understanding how genetic variation influences plant growth is important for both evolutionary and mechanistic studies. We used natural populations of Arabidopsis thaliana to identify sequence variation in a promoter region of Arabidopsis accessions that mediated differences in the expression of a previously uncharacterised membrane protein. This variation contributed to altered auxin responses and cell size during petal growth.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 242-242
Author(s):  
Olivier Decaux ◽  
Monique Clement ◽  
Florence Magrangeas ◽  
Laurence Lode ◽  
Catherine Charbonnel ◽  
...  

Abstract Pharmacogenomic profiles of genes involved in bortezomib - dexamethasone response may help to understand resistance and could provide new therapeutic targets as well as contributing to novel prognostic markers in multiple myeloma. We have used gene expression profiling to analyze the complex signaling pathways regulating the response to bortezomib - dexamethasone. Gene expression profiles were established in 9 cell lines, derived from 9 myeloma patients, incubated or not with a combination of bortezomib 10 nM and dexamethasone 1 μM. These concentrations correspond to the ones used for patients in the IFM 2005-01. Cells were collected after 6 hours of treatment. We focused our interest in early response genes, making the hypothesis that the comprehension of early effects would help to better understand the mechanisms of resistance that take place in at least two third of myeloma patients. Supervised analysis with permutations identified significantly up regulated genes involved in stress responses (heat shocks proteins, RTP801/dig2/REDD1/DDIT4), endoplasmic reticulum stress (HERP/HERPUD1, gadd145/CHOP/DDIT3), ubiquitin/proteasome pathway (proteasome 26S subunits PSMB7, PSMC4, PSMD3 and PSMD13), unfolded protein response (such as SQSTM1, ATF4) or redox equilibrium (PLRX, PRDX1). We assumed that these genes might represent a molecular signature of response to bortezomib and provide important insight into the complex mechanisms of action of these drugs. We focused on REDD1 a gene cloned in 2002 that is known to be rapidly induced by a wide variety of stress conditions (arsenic, hypoxia, dexamethasone, thapsigargin, tunimycin and heat shock) and DNA damages (ionizing radiation, ultraviolet radiation, DNA alkylant). We found that both REDD1 gene and protein expression were early and highly induced after bortezomib exposure alone or in combinaison with dexamethasone. This effect was dependent upon cell line: REDD1 was overexpressed within two hours in resistant cell lines in association with a cell size decrease while in sensitive cell lines, neither REDD1 induction nor morphological changes occured. REDD1 induction was associated with the dephosphorylation of S6K1, a key substrat of mTOR, a protein kinase which controls cell growth and cell size in response to various signals. SiRNA studies confirmed that bortezomib lead to a negative regulation of mRTor activity mediated by REDD1: disruption of REDD1 abrogates both S6K1 phosphorylation and early transitory cell size reduction. Our results are in accordance with data obtained in mouse showing an early regulation of mTOR pathway and cellular proliferation induced by REDD1 expression in response to stress. Our study suggests that mTOR regulation could be a resistance mechanism mediated by REDD1 expression. As we found that REDD1 was differentially induced in primary plasma cells from patients, this gene expression could help to predict response to bortezomib. Our objective is now to clarify the pathway that links bortezomib to REDD1 in multiple myeloma and to investigate REDD1 expression in patients enrolled in IFM 2005-01 clinical trial.


1993 ◽  
Vol 113 (8) ◽  
pp. 537-555
Author(s):  
Masaaki TSUDA

2010 ◽  
Vol 285 (15) ◽  
pp. 11297-11307 ◽  
Author(s):  
Vladimir Majerciak ◽  
Michael Kruhlak ◽  
Pradeep K. Dagur ◽  
J. Philip McCoy ◽  
Zhi-Ming Zheng

2021 ◽  
Vol 18 (178) ◽  
pp. 20210274
Author(s):  
Philipp Thomas ◽  
Vahid Shahrezaei

The chemical master equation and the Gillespie algorithm are widely used to model the reaction kinetics inside living cells. It is thereby assumed that cell growth and division can be modelled through effective dilution reactions and extrinsic noise sources. We here re-examine these paradigms through developing an analytical agent-based framework of growing and dividing cells accompanied by an exact simulation algorithm, which allows us to quantify the dynamics of virtually any intracellular reaction network affected by stochastic cell size control and division noise. We find that the solution of the chemical master equation—including static extrinsic noise—exactly agrees with the agent-based formulation when the network under study exhibits stochastic concentration homeostasis , a novel condition that generalizes concentration homeostasis in deterministic systems to higher order moments and distributions. We illustrate stochastic concentration homeostasis for a range of common gene expression networks. When this condition is not met, we demonstrate by extending the linear noise approximation to agent-based models that the dependence of gene expression noise on cell size can qualitatively deviate from the chemical master equation. Surprisingly, the total noise of the agent-based approach can still be well approximated by extrinsic noise models.


2018 ◽  
Author(s):  
Nairita Maitra ◽  
Jayamani Anandhakumar ◽  
Heidi M. Blank ◽  
Craig D. Kaplan ◽  
Michael Polymenis

ABSTRACTThe question of what determines whether cells are big or small has been the focus of many studies because it is thought that such determinants underpin the coupling of cell growth with cell division. In contrast, what determines the overall pattern of how cell size is distributed within a population of wild type or mutant cells has received little attention. Knowing how cell size varies around a characteristic pattern could shed light on the processes that generate such a pattern and provide a criterion to identify its genetic basis. Here, we show that cell size values of wild type Saccharomyces cerevisiae cells fit a gamma distribution, in haploid and diploid cells, and under different growth conditions. To identify genes that influence this pattern, we analyzed the cell size distributions of all single-gene deletion strains in Saccharomyces cerevisiae. We found that yeast strains which deviate the most from the gamma distribution are enriched for those lacking gene products functioning in gene expression, especially those in transcription or transcription-linked processes. We also show that cell size is increased in mutants carrying altered activity substitutions in Rpo21p/Rpb1, the largest subunit of RNA polymerase II (Pol II). Lastly, the size distribution of cells carrying extreme altered activity Pol II substitutions deviated from the expected gamma distribution. Our results are consistent with the idea that genetic defects in widely acting transcription factors or Pol II itself compromise both cell size homeostasis and how the size of individual cells is distributed in a population.


2017 ◽  
Author(s):  
Anissa Guillemin ◽  
Angelique Richard ◽  
Sandrine Gonin-Giraud ◽  
Olivier Gandrillon

AbstractRecent rise of single-cell studies revealed the importance of understanding the role of cell-to-cell variability, especially at the transcriptomic level. One of the numerous sources of cell-to-cell variation in gene expression is the heterogeneity in cell proliferation state. How cell cycle and cell size influences gene expression variability at single-cell level is not yet clearly understood. To deconvolute such influences, most of the single-cell studies used dedicated methods that could include some bias. Here, we provide a universal and automatic toxic-free label method, compatible with single-cell high-throughput RT-qPCR. This led to an unbiased gene expression analysis and could be also used for improving single-cell tracking and imaging when combined with cell isolation. As an application for this technique, we showed that cell-to-cell variability in chicken erythroid progenitors was negligibly influenced by cell size nor cell cycle.


2019 ◽  
Author(s):  
Richik Nilay Mukherjee ◽  
Jérémy Sallé ◽  
Serge Dmitrieff ◽  
Katherine Nelson ◽  
John Oakey ◽  
...  

SUMMARYNuclear size plays pivotal roles in gene expression, embryo development, and disease. A central hypothesis in organisms ranging from yeast to vertebrates is that nuclear size scales to cell size. This implies that nuclei may reach steady state sizes set by limiting cytoplasmic pools of size-regulating components. By monitoring nuclear dynamics in early sea urchin embryos, we found that nuclei undergo substantial growth in each interphase, reaching a maximal size prior to mitosis that declined steadily over the course of development. Manipulations of cytoplasmic volume through multiple chemical and physical means ruled out cell size as a major determinant of nuclear size and growth. Rather, our data suggest that the perinuclear endoplasmic reticulum, accumulated through dynein activity, serves as a limiting membrane pool that sets nuclear surface growth rate. Partitioning of this local pool at each cell division modulates nuclear growth kinetics and dictates size scaling throughout early development.


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