These data imply that label-retaining, premalignant cells were not out of the cell cycle during passage, but nevertheless retained their original DNA label.
The G1 cell cycle checkpoint controls passage of cells from the first gap (G) phase into the DNA synthesis (S) phase.
It is well known that multiple factors have a very strong influence on cellular stiffness even including the phase within the cell cycle or the passage number.
In addition to these either developmentally regulated or artificially induced phenotype changes that are accompanied by distinct transcriptional changes, a transcriptome of any given cell type can vary substantially depending on cell cycle [ 1- 3], passage number, and environmental factors such as oxygen concentration [ 4], temperature, and presence of serum [ 5].
Cellular proliferation is driven by progression of cells through the cell cycle consisting of sequential passage through G1, S, G2 and M phases.
Many agents used to treat AML promote double stranded DNA breaks resulting in activation of cell cycle checkpoints which suspend passage through the cell cycle and allow time for DNA repair [45] [48].
(A) Growth curve showing the population doubling of MSCs, n = 3. (B) Cell cycle analysis of MSCs at passage 3 and passage 9. Data were presented as mean ± SEM, n = 3. (C) Analysis of clonal expansion abilities of WT, heterozygous (LMNAG608G/+), homozygous (LMNAG608G/G608G) and WRN−/− MSCs.
To investigate the effects of replicative senescence on genomic integrity, we first analyzed cell cycle profiles at several passages.
Phosphorylation of pocket proteins via activated cyclin CDK complexes results in release of E2F transcription factors, allowing for passage through cell cycle checkpoints (Beijersbergen et al., 1995; Dimova and Dyson, 2005).
Next, we characterized the effect of hEB passaging on cell cycle and apoptosis.
Cell cycle and Q-banding karyotypic analysis at early passages (passage 2 8) showed that aneuploidy and chromosomal aberrations frequently occur in NPC-TDCC (Figure 4).
