scholarly journals The expanding implications of polyploidy

2015 ◽  
Vol 209 (4) ◽  
pp. 485-491 ◽  
Author(s):  
Kevin P. Schoenfelder ◽  
Donald T. Fox
Keyword(s):  
Cell Size ◽  
Recent Progress ◽  
Environmental Stresses ◽  
Polyploid Cells ◽  
Diploid Cells ◽  
Metabolic Output

Polyploid cells, which contain more than two genome copies, occur throughout nature. Beyond well-established roles in increasing cell size/metabolic output, polyploidy can also promote nonuniform genome, transcriptome, and metabolome alterations. Polyploidy also frequently confers resistance to environmental stresses not tolerated by diploid cells. Recent progress has begun to unravel how this fascinating phenomenon contributes to normal physiology and disease.

scholarly journals Transcriptome analysis of tetraploid cells identifies cyclin D2 as a facilitator of adaptation to genome doubling in the presence of p53

2016 ◽  
Vol 27 (20) ◽  
pp. 3065-3084 ◽  
Author(s):  
Tamara A. Potapova ◽  
Christopher W. Seidel ◽  
Andrew C. Box ◽  
Giulia Rancati ◽  
Rong Li
Keyword(s):  
Gene Expression ◽  
Transcriptome Analysis ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
Single Cells ◽  
Cyclin D2 ◽  
Genome Doubling ◽  
Polyploid Cells ◽  
Diploid Cells ◽  
P53 Target Genes

Tetraploidization, or genome doubling, is a prominent event in tumorigenesis, primarily because cell division in polyploid cells is error-prone and produces aneuploid cells. This study investigates changes in gene expression evoked in acute and adapted tetraploid cells and their effect on cell-cycle progression. Acute polyploidy was generated by knockdown of the essential regulator of cytokinesis anillin, which resulted in cytokinesis failure and formation of binucleate cells, or by chemical inhibition of Aurora kinases, causing abnormal mitotic exit with formation of single cells with aberrant nuclear morphology. Transcriptome analysis of these acute tetraploid cells revealed common signatures of activation of the tumor-suppressor protein p53. Suppression of proliferation in these cells was dependent on p53 and its transcriptional target, CDK inhibitor p21. Rare proliferating tetraploid cells can emerge from acute polyploid populations. Gene expression analysis of single cell–derived, adapted tetraploid clones showed up-regulation of several p53 target genes and cyclin D2, the activator of CDK4/6/2. Overexpression of cyclin D2 in diploid cells strongly potentiated the ability to proliferate with increased DNA content despite the presence of functional p53. These results indicate that p53-mediated suppression of proliferation of polyploid cells can be averted by increased levels of oncogenes such as cyclin D2, elucidating a possible route for tetraploidy-mediated genomic instability in carcinogenesis.

scholarly journals Polyploidy in the adult Drosophila brain

2019 ◽  
Author(s):  
Shyama Nandakumar ◽  
Olga Grushko ◽  
Laura A. Buttitta
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Protective Role ◽  
Adult Brain ◽  
Exogenous Dna ◽  
Damage Response ◽  
Polyploid Cells ◽  
Drosophila Brain ◽  
Accumulation Of Damage ◽  
Diploid Cells

AbstractLong-lived cells such as terminally differentiated postmitotic neurons and glia must cope with the accumulation of damage over the course of an animal’s lifespan. How long-lived cells deal with ageing-related damage is poorly understood. Here we show that polyploid cells accumulate in the ageing adult fly brain and that polyploidy protects against DNA damage-induced cell death. Multiple types of neurons and glia that are diploid at eclosion, become polyploid with age in the adult Drosophila brain. The optic lobes exhibit the highest levels of polyploidy, associated with an elevated DNA damage response in this brain region with age. Inducing oxidative stress or exogenous DNA damage leads to an earlier onset of polyploidy, and polyploid cells in the adult brain are more resistant to DNA damage-induced cell death than diploid cells. Our results suggest polyploidy may serve a protective role for neurons and glia in ageing Drosophila melanogaster brains.

scholarly journals Perturbations of transcription and gene expression-associated processes alter distribution of cell size values in Saccharomyces cerevisiae

2018 ◽  
Author(s):  
Nairita Maitra ◽  
Jayamani Anandhakumar ◽  
Heidi M. Blank ◽  
Craig D. Kaplan ◽  
Michael Polymenis
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Rna Polymerase Ii ◽  
Cell Size ◽  
Gamma Distribution ◽  
Single Gene ◽  
Growth Conditions ◽  
Wild Type ◽  
Pol Ii ◽  
Diploid Cells

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.

scholarly journals Polyploidy in the adult Drosophila brain

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Shyama Nandakumar ◽  
Olga Grushko ◽  
Laura A Buttitta
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Protective Role ◽  
Adult Brain ◽  
Exogenous Dna ◽  
Damage Response ◽  
Polyploid Cells ◽  
Drosophila Brain ◽  
Accumulation Of Damage ◽  
Diploid Cells

Long-lived cells such as terminally differentiated postmitotic neurons and glia must cope with the accumulation of damage over the course of an animal’s lifespan. How long-lived cells deal with ageing-related damage is poorly understood. Here we show that polyploid cells accumulate in the adult fly brain and that polyploidy protects against DNA damage-induced cell death. Multiple types of neurons and glia that are diploid at eclosion, become polyploid in the adult Drosophila brain. The optic lobes exhibit the highest levels of polyploidy, associated with an elevated DNA damage response in this brain region. Inducing oxidative stress or exogenous DNA damage leads to an earlier onset of polyploidy, and polyploid cells in the adult brain are more resistant to DNA damage-induced cell death than diploid cells. Our results suggest polyploidy may serve a protective role for neurons and glia in adult Drosophila melanogaster brains.

scholarly journals Synergistic CDK control pathways maintain cell size homeostasis

2020 ◽  
Author(s):  
James O. Patterson ◽  
Souradeep Basu ◽  
Paul Rees ◽  
Paul Nurse
Keyword(s):  
Cell Division ◽  
Cell Size ◽  
High Throughput ◽  
Small Cells ◽  
Control Network ◽  
Size Information ◽  
Division Cell ◽  
Diploid Cells ◽  
High Cyclin

AbstractTo coordinate cell size with cell division, cell size must be computed by the cyclin-CDK control network to trigger division appropriately. Here we dissect determinants of cyclin-CDK activity using a novel high-throughput single-cell in vivo system. We show that inhibitory phosphorylation of CDK encodes cell size information and works synergistically with PP2A to prevent division in smaller cells. However, even in the absence of all canonical regulators of cyclin-CDK, small cells with high cyclin-CDK levels are restricted from dividing. We find that diploid cells of equivalent size to haploid cells exhibit lower CDK activity in response to equal cyclin-CDK enzyme concentrations, suggesting that CDK activity is reduced by DNA concentration. Thus, multiple pathways directly regulate cyclin-CDK activity to maintain robust cell size homeostasis.

scholarly journals The structure of heterochromatic DNA is altered in polyploid cells of Drosophila melanogaster.

1997 ◽  
Vol 17 (3) ◽  
pp. 1254-1263 ◽  
Author(s):  
R L Glaser ◽  
T J Leach ◽  
S E Ostrowski
Keyword(s):  
Drosophila Melanogaster ◽  
Salivary Gland ◽  
Dna Sequences ◽  
Dna Molecules ◽  
Restriction Fragments ◽  
General Consequence ◽  
Polyploid Cells ◽  
Chromosome Formation ◽  
Chromosome Iii ◽  
Diploid Cells

DNA sequences within heterochromatin are often selectively underrepresented during development of polyploid chromosomes, and DNA molecules of altered structure are predicted to form as a consequence of the underrepresentation process. We have identified heterochromatic DNAs of altered structure within sequences that are underrepresented in polyploid cells of Drosophila melanogaster. Specifically, restriction fragments that extend into centric heterochromatin of the minichromosome Dp(1;f)1187 are shortened in polyploid cells of both the ovary and salivary gland but not in the predominantly diploid cells of the embryo or larval imaginal discs and brains. Shortened DNA molecules were also identified within heterochromatic sequences of chromosome III. These results suggest that the structure of heterochromatic DNA is altered as a general consequence of polyploid chromosome formation and that the shortened molecules identified form as a consequence of heterochromatic underrepresentation. Finally, alteration of heterochromatic DNA structure on Dp(1;f)1187 was not correlated with changes in the variegated expression of the yellow gene located on the minichromosome.

Polysomaty and somatic reduction in Phaseolus coccineus L.

Genome ◽  
1988 ◽  
Vol 30 (5) ◽  
pp. 671-676 ◽  
Author(s):  
A. Cavallini ◽  
R. Cremonini ◽  
G. Cionini ◽  
P. G. Cionini
Keyword(s):  
De Novo ◽  
Root Apex ◽  
Phaseolus Coccineus ◽  
Homologous Chromosomes ◽  
Chromosome Endoreduplication ◽  
Early Embryos ◽  
Pertinent Data ◽  
Polyploid Cells ◽  
Diploid Cells ◽  
Shoot Meristems

By means of karyological, cytophotometric, and autoradiographic analyses it has been shown that, owing to alterations in the DNA synthesis – mitosis sequence, cells with different nuclear conditions are continuously formed de novo and proliferate in Phaseolus coccineus meristems. Besides diploid cells, the following also occur: (i) polyploid cells as the result of chromosome endoreduplication followed by mitosis; (ii) haploid cells as the result of the separation of the two groups of homologous chromosomes in cells that have omitted DNA reduplication; and (iii) since haploid cells undergo chromosome endoreduplication and divide, isogenic cells can be produced. Diploid mitoses alone are present in the meristems of early embryos; haploid mitoses first appear in both root and shoot meristems with increasing embryo development, followed later by cells undergoing chromosome endoreduplication. The study of the root apex has shown that neither polyploid nor reduced cells occur with the same frequency in its various portions. These results are discussed in relation to pertinent data in the literature and the mechanisms responsible for the occurrence of polysomaty and somatic reduction are suggested.Key words: isogenic cells, Phaseolus coccineus, polysomaty, somatic reduction.

scholarly journals Evaluation of mitotic activity in tapetal cells of grapevine (Vitis L.)

2021 ◽  
Vol 49 (2) ◽  
pp. 11975
Author(s):  
Neiva Izabel PIEROZZI ◽  
Mara FERNANDES MOURA
Keyword(s):  
Mitotic Activity ◽  
Meiotic Stage ◽  
Polyploid Cells ◽  
Cytogenetic Studies ◽  
Tapetal Cells ◽  
Diploid Cells ◽  
Chromosome Spreading ◽  
Interesting Alternative ◽  
Large Nucleolus

The knowledge with reference to the grapevine tapetum has been centered on its anatomy/morphology and hardly anything at all is known about its mitotic activity throughout the microsporogenesis. The aim of this study was to ascertain the mitotic activity in tapetal cells of some grapevines (Vitis L.) broadening knowledge about this tissue and simultaneously corroborating the viability of its use as an alternative tissue for further cytogenetic studies. Young buds of 12 grapevine varieties at different meiotic stages were squashed and tapetal cells a prometaphase/metaphase scored in each meiotic stage. Mitotic activity was observed since the beginning of microsporogenesis, where it was more intense, decreasing toward tetrad. Polyploid tapetal cells arose through endomitosis while the microsporogenesis advanced. Two types of polyploid cells were evidenced, those with two or more individualized diploid chromosome groups and those with only one polyploid group. The percentage of diploid cells and of polyploid cells with two or more individualized diploid groups was higher during the first stage of microsporogenesis, though decreasing and giving way to cells with one large polyploid group as microsporogenesis moved toward tetrad. The nucleolus number was scored at interphase at different stages. Two and four nucleoli prevailed in tapetal cells at all stages except at tetrad where one large nucleolus was seen. The results showed that despite of the squashing technique applied, grapevine tapetum has a substantial amount of cells with mitotic activity with a satisfactory chromosome spreading therefore establishing an interesting alternative and promising tissue for later cytomolecular studies.

scholarly journals CDK control pathways integrate cell size and ploidy information to control cell division

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
James Oliver Patterson ◽  
Souradeep Basu ◽  
Paul Rees ◽  
Paul Nurse
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Size ◽  
Control Cell ◽  
Size Information ◽  
Inhibitory Tyrosine Phosphorylation ◽  
Dependent Inhibition ◽  
Control Cell Division ◽  
Diploid Cells

Maintenance of cell size homeostasis is a property that is conserved throughout eukaryotes. Cell size homeostasis is brought about by the co-ordination of cell division with cell growth, and requires restriction of smaller cells from undergoing mitosis and cell division, whilst allowing larger cells to do so. Cyclin-CDK is the fundamental driver of mitosis and therefore ultimately ensures size homeostasis. Here we dissect determinants of CDK activity in vivo to investigate how cell size information is processed by the cell cycle network in fission yeast. We develop a high-throughput single-cell assay system of CDK activity in vivo and show that inhibitory tyrosine phosphorylation of CDK encodes cell size information, with the phosphatase PP2A aiding to set a size threshold for division. CDK inhibitory phosphorylation works synergistically with PP2A to prevent mitosis in smaller cells. Finally, we find that diploid cells of equivalent size to haploid cells exhibit lower CDK activity in response to equal cyclin-CDK enzyme concentrations, suggesting that CDK activity is reduced by increased DNA levels. Therefore, scaling of cyclin-CDK levels with cell size, CDK inhibitory phosphorylation, PP2A, and DNA-dependent inhibition of CDK activity, all inform the cell cycle network of cell size, thus contributing to cell-size homeostasis.

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