Cellular and nuclear volume of human cells during the cell cycle

Fidorra, J.; Mielke, Th.; Booz, J.; Feinendegen, L. E.

doi:10.1007/bf01324188

Cited by 36 publications

(29 citation statements)

References 18 publications

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“…3 B and C). Because in Arabidopsis shoot apices G1, S, and G2, phases have been reported to last for ∼50%, ∼25%, and ∼15% of the cell cycle (42), our data imply that nuclei grow through each of these phases, as in other organisms (43,44). Following an asymmetrical division, the small daughter grew at a faster rate per unit size than the large daughter …”

Section: Discussionmentioning

confidence: 55%

Cell size and growth regulation in the Arabidopsis thaliana apical stem cell niche

Willis

Refahi

Wightman

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

187

217

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Cell size and growth kinetics are fundamental cellular properties with important physiological implications. Classical studies on yeast, and recently on bacteria, have identified rules for cell size regulation in single cells, but in the more complex environment of multicellular tissues, data have been lacking. In this study, to characterize cell size and growth regulation in a multicellular context, we developed a 4D imaging pipeline and applied it to track and quantify epidermal cells over 3-4 d in Arabidopsis thaliana shoot apical meristems. We found that a cell size checkpoint is not the trigger for G2/M or cytokinesis, refuting the unexamined assumption that meristematic cells trigger cell cycle phases upon reaching a critical size. Our data also rule out models in which cells undergo G2/M at a fixed time after birth, or by adding a critical size increment between G2/M transitions. Rather, cell size regulation was intermediate between the critical size and critical increment paradigms, meaning that cell size fluctuations decay by ∼75% in one generation compared with 100% (critical size) and 50% (critical increment). Notably, this behavior was independent of local cell-cell contact topologies and of position within the tissue. Cells grew exponentially throughout the first >80% of the cell cycle, but following an asymmetrical division, the small daughter grew at a faster exponential rate than the large daughter, an observation that potentially challenges present models of growth regulation. These growth and division behaviors place strong constraints on quantitative mechanistic descriptions of the cell cycle and growth control.cell size | cell growth | cell cycle | homeostasis | plant stem cells H ow cells coordinate growth and division to achieve a particular cell size remains a fundamental question in biology. Our understanding of this basic property of cells is limited, in part, by the lack of quantitative data on cellular growth and size kinetics over multiple generations, especially in higher eukaryotes (1). Classical studies of cell size homeostasis focused on whether division occurred upon reaching a critical size or after a fixed time period has elapsed (2, 3). However, time-lapse studies of single-celled organisms spanning a range of bacteria (4-7) and the yeast Saccharomyces cerevisiae (8) have recently indicated that cell size is regulated by the addition of a fixed volume increment between divisions. Identification of the size regulation behavior constrains the set of feasible molecular scenarios for how growth and division are coordinated with the cell cycle (8-10). In multicellular tissues, the loss of growth and division/cell cycle coordination could have an impact on the organism's development, yet, to the best of our knowledge, cell growth and size kinetics have never before been measured over generations in a tissue context. The experimental challenges are particularly acute because interdivision times are often on the order of tens of hours, cells have a diversity of shapes necessitating di...

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Section: Discussionmentioning

confidence: 55%

Cell size and growth regulation in the Arabidopsis thaliana apical stem cell niche

Willis

Refahi

Wightman

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

187

217

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“…Nuclear cross sectional area is known to correlate with cell cycle stage (28). Comparing the nuclear areas of cells that formed foci after laser exposure (n ϭ 31, Fig.…”

Section: Resultsmentioning

confidence: 99%

Double-strand DNA breaks recruit the centromeric histone CENP-A

Zeitlin¹,

Baker²,

Chapados

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

134

129

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The histone H3 variant CENP-A is required for epigenetic specification of centromere identity through a loading mechanism independent of DNA sequence. Using multiphoton absorption and DNA cleavage at unique sites by I-SceI endonuclease, we demonstrate that CENP-A is rapidly recruited to double-strand breaks in DNA, along with three components (CENP-N, CENP-T, and CENP-U) associated with CENP-A at centromeres. The centromere-targeting domain of CENP-A is both necessary and sufficient for recruitment to double-strand breaks. CENP-A accumulation at DNA breaks is enhanced by active non-homologous end-joining but does not require DNA-PKcs or Ligase IV, and is independent of H2AX. Thus, induction of a double-strand break is sufficient to recruit CENP-A in human and mouse cells. Finally, since cell survival after radiation-induced DNA damage correlates with CENP-A expression level, we propose that CENP-A may have a function in DNA repair.

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“…Nuclear volume in metazoan cells can change without alterations in cellular DNA content. A handful of studies with mammalian cells have suggested, but not convincingly demonstrated, that the nucleus may increase in volume before S-phase (Maul et al, 1972;Yen and Pardee, 1979;Fidorra et al, 1981). It is evident in many animal embryos that nuclear volume shrinks during embryonic cleavage cycles as cell volume decreases (Wilson, 1925;Gerhart, 1980;Sulston et al, 1983).…”

Section: Discussionmentioning

confidence: 99%

The Size of the Nucleus Increases as Yeast Cells Grow

Jorgensen

Edgington

Schneider

et al. 2007

MBoC

378

339

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It is not known how the volume of the cell nucleus is set, nor how the ratio of nuclear volume to cell volume (N/C) is determined. Here, we have measured the size of the nucleus in growing cells of the budding yeast Saccharomyces cerevisiae. Analysis of mutant yeast strains spanning a range of cell sizes revealed that the ratio of average nuclear volume to average cell volume was quite consistent, with nuclear volume being ϳ7% that of cell volume. At the single cell level, nuclear and cell size were strongly correlated in growing wild-type cells, as determined by three different microscopic approaches. Even in G1-phase, nuclear volume grew, although it did not grow quite as fast as overall cell volume. DNA content did not appear to have any immediate, direct influence on nuclear size, in that nuclear size did not increase sharply during S-phase. The maintenance of nuclear size did not require continuous growth or ribosome biogenesis, as starvation and rapamycin treatment had little immediate impact on nuclear size. Blocking the nuclear export of new ribosomal subunits, among other proteins and RNAs, with leptomycin B also had no obvious effect on nuclear size. Nuclear expansion must now be factored into conceptual and mathematical models of budding yeast growth and division. These results raise questions as to the unknown force(s) that expand the nucleus as yeast cells grow.

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Cellular and nuclear volume of human cells during the cell cycle

Cited by 36 publications

References 18 publications

Cell size and growth regulation in the Arabidopsis thaliana apical stem cell niche

Cell size and growth regulation in the Arabidopsis thaliana apical stem cell niche

Double-strand DNA breaks recruit the centromeric histone CENP-A

The Size of the Nucleus Increases as Yeast Cells Grow

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