scholarly journals Release from cell cycle arrest with Cdk4/6 inhibitors generates highly synchronized cell cycle progression in human cell culture

Open Biology ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 200200
Author(s):  
Eleanor Wendy Trotter ◽  
Iain Michael Hagan
Keyword(s):  
Cell Cycle ◽  
Human Cell ◽  
Cell Cycle Progression ◽  
Control Point ◽  
Cell Cycle Regulators ◽  
Human Cell Culture ◽  
Cycle Progression ◽  
Restriction Point ◽  
Cycle Arrest ◽  
Arrest Cell Cycle Progression

Each approach used to synchronize cell cycle progression of human cell lines presents a unique set of challenges. Induction synchrony with agents that transiently block progression through key cell cycle stages are popular, but change stoichiometries of cell cycle regulators, invoke compensatory changes in growth rate and, for DNA replication inhibitors, damage DNA. The production, replacement or manipulation of a target molecule must be exceptionally rapid if the interpretation of phenotypes in the cycle under study is to remain independent of impacts upon progression through the preceding cycle. We show how these challenges are avoided by exploiting the ability of the Cdk4/6 inhibitors, palbociclib, ribociclib and abemaciclib to arrest cell cycle progression at the natural control point for cell cycle commitment: the restriction point. After previous work found no change in the coupling of growth and division during recovery from CDK4/6 inhibition, we find high degrees of synchrony in cell cycle progression. Although we validate CDK4/6 induction synchronization with hTERT-RPE-1, A549, THP1 and H1299, it is effective in other lines and avoids the DNA damage that accompanies synchronization by thymidine block/release. Competence to return to cycle after 72 h arrest enables out of cycle target induction/manipulation, without impacting upon preceding cycles.

scholarly journals Release from cell cycle arrest with Cdk4/6 inhibitors generates highly synchronised cell cycle progression in human cell culture

2020 ◽  
Author(s):  
Eleanor Wendy Trotter ◽  
Iain Michael Hagan
Keyword(s):  
Cell Cycle ◽  
Human Cell ◽  
Cell Cycle Progression ◽  
Control Point ◽  
Cell Cycle Regulators ◽  
Human Cell Culture ◽  
Cycle Progression ◽  
Restriction Point ◽  
Cycle Arrest ◽  
Arrest Cell Cycle Progression

AbstractEach approach used to synchronise cell cycle progression of human cell lines presents a unique set of challenges. Induction synchrony with agents that transiently block progression through key cell cycle stages are popular, but change stoichiometries of cell cycle regulators, invoke compensatory changes in growth rate and, for DNA replication inhibitors, damage DNA. The production, replacement, or manipulation of a target molecule must be exceptionally rapid if the interpretation of phenotypes in the cycle under study are to remain independent of impacts upon progression through the preceding cycle. We show how these challenges are avoided by exploiting the ability of the Cdk4/6 inhibitors, palbociclib, ribociclib and abemaciclib to arrest cell cycle progression at the natural control point for cell cycle commitment: the restriction point. After previous work found no change in the coupling of growth and division during recovery from CDK4/6 inhibition, we find high degrees of synchrony in cell cycle progression. Although we validate CDK4/6 induction synchronisation with hTERT-RPE-1, THP1 and H1299, it is effective in other lines and avoids the DNA damage that accompanies synchronisation by thymidine block/release. Competence to return to cycle after 72 hours arrest enables out of cycle target induction/manipulation, without impacting upon preceding cycles.

Coordinate developmental control of the meiotic cell cycle and spermatid differentiation in Drosophila males

Development ◽  
1996 ◽  
Vol 122 (4) ◽  
pp. 1331-1341 ◽  
Author(s):  
T.Y. Lin ◽  
S. Viswanathan ◽  
C. Wood ◽  
P.G. Wilson ◽  
N. Wolf ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Control Point ◽  
Meiotic Cell ◽  
Wild Type ◽  
Meiotic Arrest ◽  
Cycle Progression ◽  
Cycle Arrest ◽  
Secondary Consequence ◽  
Meiosis I

Wild-type function of four Drosophila genes, spermatocyte arrest, cannonball, always early and meiosis I arrest, is required both for cell-cycle progression through the G2/M transition of meiosis I in males and for onset of spermatid differentiation. In males mutant for any one of these meiotic arrest genes, mature primary spermatocytes with partially condensed chromosomes accumulate and postmeiotic cells are lacking. The arrest in cell-cycle progression occurs prior to degradation of cyclin A protein. The block in spermatogenesis in these mutants is not simply a secondary consequence of meiotic cell-cycle arrest, as spermatid differentiation proceeds in males mutant for the cell cycle activating phosphatase twine. Instead, the arrest of both meiosis and spermiogenesis suggests a control point that may serve to coordinate the male meiotic cell cycle with the spermatid differentiation program. The phenotype of the Drosophila meiotic arrest mutants is strikingly similar to the histopathological features of meiosis I maturation arrest infertility in human males, suggesting that the control point may be conserved from flies to man.

scholarly journals Hyperbaric oxygen promotes not only glioblastoma proliferation but also chemosensitization by inhibiting HIF1α/HIF2α-Sox2

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Pan Wang ◽  
Sheng Gong ◽  
Jinyu Pan ◽  
Junwei Wang ◽  
Dewei Zou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Hyperbaric Oxygen ◽  
Cell Cycle Progression ◽  
Malignant Progression ◽  
Cycle Progression ◽  
Chemotherapy Sensitivity ◽  
Hypoxic Conditions ◽  
Cycle Arrest

AbstractThere exists a consensus that combining hyperbaric oxygen (HBO) and chemotherapy promotes chemotherapy sensitivity in GBM cells. However, few studies have explored the mechanism involved. HIF1α and HIF2α are the two main molecules that contribute to GBM malignant progression by inhibiting apoptosis or maintaining stemness under hypoxic conditions. Moreover, Sox2, a marker of stemness, also contributes to GBM malignant progression through stemness maintenance or cell cycle arrest. Briefly, HIF1α, HIF2α and Sox2 are highly expressed under hypoxia and contribute to GBM growth and chemoresistance. However, after exposure to HBO for GBM, whether the expression of the above factors is decreased, resulting in chemosensitization, remains unknown. Therefore, we performed a series of studies and determined that the expression of HIF1α, HIF2α and Sox2 was decreased after HBO and that HBO promoted GBM cell proliferation through cell cycle progression, albeit with a decrease in stemness, thus contributing to chemosensitization via the inhibition of HIF1α/HIF2α-Sox2.

scholarly journals Influenza A Virus Replication Induces Cell Cycle Arrest in G0/G1 Phase

2010 ◽  
Vol 84 (24) ◽  
pp. 12832-12840 ◽  
Author(s):  
Yuan He ◽  
Ke Xu ◽  
Bjoern Keiner ◽  
Jianfang Zhou ◽  
Volker Czudai ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Influenza A Virus ◽  
Influenza A ◽  
Cell Cycle Progression ◽  
Virus Production ◽  
Phase Cell ◽  
Cycle Progression ◽  
Cycle Arrest ◽  
Infected Cells

ABSTRACT Many viruses interact with the host cell division cycle to favor their own growth. In this study, we examined the ability of influenza A virus to manipulate cell cycle progression. Our results show that influenza A virus A/WSN/33 (H1N1) replication results in G0/G1-phase accumulation of infected cells and that this accumulation is caused by the prevention of cell cycle entry from G0/G1 phase into S phase. Consistent with the G0/G1-phase accumulation, the amount of hyperphosphorylated retinoblastoma protein, a necessary active form for cell cycle progression through late G1 into S phase, decreased after infection with A/WSN/33 (H1N1) virus. In addition, other key molecules in the regulation of the cell cycle, such as p21, cyclin E, and cyclin D1, were also changed and showed a pattern of G0/G1-phase cell cycle arrest. It is interesting that increased viral protein expression and progeny virus production in cells synchronized in the G0/G1 phase were observed compared to those in either unsynchronized cells or cells synchronized in the G2/M phase. G0/G1-phase cell cycle arrest is likely a common strategy, since the effect was also observed in other strains, such as H3N2, H9N2, PR8 H1N1, and pandemic swine H1N1 viruses. These findings, in all, suggest that influenza A virus may provide favorable conditions for viral protein accumulation and virus production by inducing a G0/G1-phase cell cycle arrest in infected cells.

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