scholarly journals Scaling of G1 duration with population doubling time by a cyclin inSaccharomyces cerevisiae

2017 ◽  
Author(s):  
Heidi M. Blank ◽  
Michelle Callahan ◽  
Ioannis P.E. Pistikopoulos ◽  
Aggeliki O. Polymenis ◽  
Michael Polymenis
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Translational Control ◽  
Doubling Time ◽  
Qualitative Description ◽  
Quantitative Relation ◽  
Population Doubling ◽  
Population Doubling Time ◽  
Specific Cell ◽  
Cell Cycle Phases

ABSTRACTThe longer cells stay in particular phases of the cell cycle, the longer it will take these cell populations to increase. However, the above qualitative description has very little predictive value, unless it can be codified mathematically. A quantitative relation that defines the population doubling time (Td) as a function of the time eukaryotic cells spend in specific cell cycle phases would be instrumental for estimating rates of cell proliferation and for evaluating introduced perturbations. Here, we show that in human cells the length of the G1 phase (TG1) regressed on Tdwith a slope of ≈0.75, while in the yeastSaccharomyces cerevisiaethe slope was slightly smaller, at ≈0.60. On the other hand, cell size was not strongly associated with Tdor TG1in cell cultures that were proliferating at different rates. Furthermore, we show that levels of the yeast G1 cyclin Cln3p were positively associated with rates of cell proliferation over a broad range, at least in part through translational control mediated by a short uORF in theCLN3transcript. Cln3p was also necessary for the proper scaling between TG1and Td. In contrast, yeast lacking the Whi5p transcriptional repressor maintained the scaling between TG1and Td. These data reveal fundamental scaling relations between the duration of eukaryotic cell cycle phases and rates of cell proliferation, point to the necessary role of Cln3p in these relations in yeast and provide a mechanistic basis linking Cln3p levels to proliferation rates and the scaling of G1 with doubling time.

scholarly journals Transcript profile distinguishes variability in human myogenic progenitor cell expansion capacity

2018 ◽  
Vol 50 (10) ◽  
pp. 817-827 ◽  
Author(s):  
Emily S. Riddle ◽  
Erica L. Bender ◽  
Anna E. Thalacker-Mercer
Keyword(s):  
Cell Cycle ◽  
Doubling Time ◽  
Growth Parameters ◽  
Principal Component ◽  
Saturation Density ◽  
Population Doubling ◽  
Population Doubling Time ◽  
Transcript Profile ◽  
Q Value ◽  
Expansion Capacity

Primary human muscle progenitor cells (hMPCs) are commonly used to understand skeletal muscle biology, including the regenerative process. Variability from unknown origin in hMPC expansion capacity occurs independently of disease, age, or sex of the donor. We sought to determine the transcript profile that distinguishes hMPC cultures with greater expansion capacity and to identify biological underpinnings of these transcriptome profile differences. Sorted (CD56+/CD29+) hMPC cultures were clustered by unbiased, K-means cluster analysis into FAST and SLOW based on growth parameters (saturation density and population doubling time). FAST had greater expansion capacity indicated by significantly reduced population doubling time (−60%) and greater saturation density (+200%), nuclei area under the curve (AUC, +250%), and confluence AUC (+120%). Additionally, FAST had fewer % dead cells AUC (−44%, P < 0.05). RNA sequencing was conducted on RNA extracted during the expansion phase. Principal component analysis distinguished FAST and SLOW based on the transcript profiles. There were 2,205 differentially expressed genes (DEgenes) between FAST and SLOW (q value ≤ 0.05); 362 DEgenes met a more stringent cut-off (q value ≤ 0.001 and 2.0 fold-change). DEgene enrichment suggested FAST (vs. SLOW) had promotion of the cell cycle, reduced apoptosis and cellular senescence, and enhanced DNA replication. Novel (RABL6, IRGM1, and AREG) and known (FOXM1, CDKN1A, Rb) genes emerged as regulators of identified functional pathways. Collectively the data suggest that variation in hMPC expansion capacity occurs independently of age and sex and is driven, in part, by intrinsic mechanisms that support the cell cycle.

scholarly journals Molecular Aspects of Adipose-Derived Stromal Cell Senescence in a Long-Term Culture: A Potential Role of Inflammatory Pathways

2020 ◽  
Vol 29 ◽  
pp. 096368972091734 ◽  
Author(s):  
Marta Pokrywczynska ◽  
Małgorzata Maj ◽  
Tomasz Kloskowski ◽  
Monika Buhl ◽  
Daria Balcerczyk ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Doubling Time ◽  
Population Doubling ◽  
Population Doubling Time ◽  
Proliferative Potential ◽  
Differentiation Potential ◽  
Long Term Culture ◽  
Stromal Stem Cells

Long-term culture of mesenchymal stromal/stem cells in vitro leads to their senescence. It is very important to define the maximal passage to which the mesenchymal stromal/stem cells maintain their regenerative properties and can be used for cellular therapies and construction of neo-organs for clinical application. Adipose-derived stromal/stem cells were isolated from porcine adipose tissue. Immunophenotype, population doubling time, viability using bromodeoxyuridine assay, MTT assay, clonogencity, β-galactosidase activity, specific senescence-associated gene expression, apoptosis, and cell cycle of adipose-derived mesenchymal stromal/stem cells (AD-MSCs) were analyzed. All analyses were performed through 12 passages (P). Decreasing viability and proliferative potential of AD-MSCs with subsequent passages together with prolonged population doubling time were observed. Expression of β-galactosidase gradually increased after P6. Differentiation potential of AD-MSCs into adipogenic, chondrogenic, and osteogenic lineages decreased at the end of culture (P10). No changes in the cell cycle, the number of apoptotic cells and expression of specific AD-MSC markers during the long-term culture were revealed. Molecular analysis showed increased expression of genes involved in activation of inflammatory response. AD-MSCs can be cultured for in vivo applications without loss of their properties up to P6.

scholarly journals Unequal division in Saccharomyces cerevisiae and its implications for the control of cell division.

1977 ◽  
Vol 75 (2) ◽  
pp. 422-435 ◽  
Author(s):  
L H Hartwell ◽  
M W Unger
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Doubling Time ◽  
Daughter Cell ◽  
Population Doubling ◽  
Population Doubling Time ◽  
Protein Synthesis Inhibitor ◽  
Parent Cell ◽  
Rate Limiting ◽  
Mating Factor

The budding yeast, Saccharomyces cerevisiae, was grown exponentially at different rates in the presence of growth rate-limiting concentrations of a protein synthesis inhibitor, cycloheximide. The volumes of the parent cell and the bud were determined as were the intervals of the cell cycle devoted to the unbudded and budded periods. We found that S. cerevisiae cells divide unequally. The daughter cell (the cell produced at division by the bud of the previous cycle) is smaller and has a longer subsequent cell cycle than the parent cell which produced it. During the budded period most of the volume increase occurs in the bud and very little in the parent cell, while during the unbudded period both the daughter and the parent cell increase significantly in volume. The length of the budded interval of the cell cycle varies little as a function of population doubling time; the unbudded interval of the parent cell varies moderately; and the unbudded interval for the daughter cell varies greatly (in the latter case an increase of 100 min in population doubling time results in an increase of 124 min in the daughter cell's unbudded interval). All of the increase in the unbudded period occurs in that interval of G1 that precedes the point of cell cycle arrest by the S. cerevisiae alpha-mating factor. These results are qualitatively consistent with and support the model for the coordination of growth and division (Johnston, G. C., J. R. Pringle, and L. H. Hartwell. 1977. Exp. Cell. Res. 105:79-98.) This model states that growth and not the events of the DNA division cycle are rate limiting for cellular proliferation and that the attainment of a critical cell size is a necessary prerequisite for the "start" event in the DNA-division cycle, the event that requires the cdc 28 gene product, is inhibited by mating factor and results in duplication of the spindle pole body.

scholarly journals Linking lineage and population observables in biological branching processes

2019 ◽  
Author(s):  
Reinaldo García-García ◽  
Arthur Genthon ◽  
David Lacoste
Keyword(s):  
Population Dynamics ◽  
Generation Time ◽  
Doubling Time ◽  
Branching Processes ◽  
Underlying Mechanism ◽  
Population Doubling ◽  
Population Doubling Time ◽  
Division Rate ◽  
Fluctuation Theorems ◽  
The Mean

Using a population dynamics inspired by an ensemble of growing cells, a set of fluctuation theorems linking observables measured at the lineage and population levels are derived. One of these relations implies inequalities comparing the population doubling time with the mean generation time at the lineage or population levels. We argue that testing these inequalities provides useful insights into the underlying mechanism controlling the division rate in such branching processes.

Paradoxically slow preadipocyte replication and differentiation in corpulent rats

1990 ◽  
Vol 258 (2) ◽  
pp. E368-E376 ◽  
Author(s):  
G. Shillabeer ◽  
J. M. Forden ◽  
J. C. Russell ◽  
D. C. Lau
Keyword(s):  
Adipose Tissue ◽  
Doubling Time ◽  
Tissue Growth ◽  
Population Doubling ◽  
Population Doubling Time ◽  
Sprague Dawley ◽  
Induced Differentiation ◽  
Sd Rats

We have investigated the in vitro rate of replication and differentiation of preadipocytes derived from lean (+/+) and obese (cp/cp) male JCR:LA-corpulent (cp) rats in an attempt to identify mechanisms that regulate adipose tissue growth. Cp/cp rats were twofold heavier than age-matched lean rats by 9-10 mo. Cp/cp-derived preadipocytes demonstrated an inherently slower rate of replication than +/+ preadipocytes (population doubling time: cp/cp 52.3 +/- 9.6 h vs. +/+ 19.7 +/- 1.6 h), although the preadipocyte pool in the cp/cp was significantly greater. Cp/cp preadipocytes were resistant to hormonally induced differentiation (19.9 +/- 9.4% of cells accumulated lipid) but differentiated when cocultured with mature adipocytes to the same extent as preadipocytes derived from Sprague-Dawley (SD) rats (cp/cp 48.4 +/- 15.2% vs. SD 52.2 +/- 11.9%). In contrast, SD preadipocytes did not differentiate in response to mature adipocytes from +/+ rats (13.8 +/- 5.2%). Our observations suggest that preadipocyte replication and maturation may not be controlled in a coordinated manner.

Impact of temperature and dissolved oxygen level on the population dynamics of naidids and their reproduction in biological activated carbon filters: a life table demographic study

2019 ◽  
Vol 19 (5) ◽  
pp. 1363-1370
Author(s):  
Xiao-Bao Nie ◽  
Yu-Qing Wu ◽  
Yuan-Nan Long ◽  
Chang-Bo Jiang ◽  
Li Kong
Keyword(s):  
Population Dynamics ◽  
Drinking Water ◽  
Activated Carbon ◽  
Life Table ◽  
Doubling Time ◽  
Population Doubling ◽  
Population Doubling Time ◽  
Biological Activated Carbon ◽  
Water Plant ◽  
Water Plants

Abstract Aquatic macro-organisms, such as naidids, propagate excessively in biological activated carbon (BAC) filters. This has become a troublesome problem for drinking water plants. For successful control of naidid contamination risk, it is necessary to determine the population dynamics under different environmental conditions within drinking water plants, with special emphasis on BAC filters. In this study, field studies of naidid distribution in a drinking water plant were conducted, and the effects of temperature and dissolved oxygen (DO) on naidid population dynamics were investigated using the life table method. The results indicated that naidid pollution in the water plant occurred seasonally and was induced by the excessive propagation of naidids in the BAC filters. Increased temperature and DO increased the naidid intrinsic rate of natural increase and decreased the naidid population doubling time. The life table method was also used to acquire the reproductive parameters of naidids in BAC filters based on simulative experiments. These results indicated that naidids can reproduce asexually in BAC filters, and the population doubling time was 12.60 days.

Adult human aortic smooth muscle cells in culture produce active TGF-beta

1993 ◽  
Vol 265 (2) ◽  
pp. C571-C576 ◽  
Author(s):  
H. L. Kirschenlohr ◽  
J. C. Metcalfe ◽  
P. L. Weissberg ◽  
D. J. Grainger
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Dna Synthesis ◽  
Doubling Time ◽  
Muscle Cells ◽  
Lung Epithelial Cells ◽  
Population Doubling ◽  
Population Doubling Time ◽  
Tgf Beta ◽  
Adult Human

Vascular smooth muscle cells (VSMC) from adult human aortas proliferated in culture in response to fetal calf serum (FCS) with a population doubling time of 70-85 h compared with 35 +/- 5 h for VSMC derived from adult rat aortas. Medium conditioned on cultures prepared from aortas from three different donors and mixed 1:1 with fresh Dulbecco's modified Eagle's medium plus 20% FCS [human conditioned medium (HCM)] reduced the rate of proliferation of rat VSMC by 46 +/- 6% (n = 3) after 48 h compared with cells in fresh medium. HCM did not reduce the proportion (> 65%) of rat VSMC that entered DNA synthesis but delayed entry into mitosis by at least 18 h. This effect was similar to previous observations of the action of transforming growth factor-beta (TGF-beta) on rat VSMC (G. K. Owens, A. A. Geisterfer, Y. W. Yang, and A. Komoriya. J. Cell Biol. 107: 771-780, 1988). A TGF-beta assay using DNA synthesis in mink lung epithelial cells confirmed that human, but not rat, VSMC in culture secrete active TGF-beta. Addition of a neutralizing antibody to TGF-beta to human VSMC in the presence of 20% FCS decreased the population doubling time from 74 +/- 3 to 46 +/- 6 h (n = 3). These observations demonstrate that the long population doubling time of human VSMC is due to the production of active TGF-beta and to an inhibitory autocrine loop.

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