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Cytometry. Part a : the Journal of the... Aug 2015
Topics: Cell Cycle; Humans
PubMed: 26211909
DOI: 10.1002/cyto.a.22721 -
Cell Reports Methods Oct 2022Populations of stem, progenitor, or cancer cells show proliferative heterogeneity , comprising proliferating and quiescent cells. Consistent quantification of the...
Populations of stem, progenitor, or cancer cells show proliferative heterogeneity , comprising proliferating and quiescent cells. Consistent quantification of the quiescent subpopulation and progression of the proliferating cells through the individual phases of the cell cycle has not been achieved. Here, we describe CycleFlow, a method that robustly infers this comprehensive information from standard pulse-chase experiments with thymidine analogs. Inference is based on a mathematical model of the cell cycle, with realistic waiting time distributions for the G, S, and G/M phases and a long-term quiescent G state. We validate CycleFlow with an exponentially growing cancer cell line . Applying it to T cell progenitors in steady state , we uncover strong proliferative heterogeneity, with a minority of CD4CD8 T cell progenitors cycling very rapidly and then entering quiescence. CycleFlow is suitable as a routine method for quantitative cell-cycle analysis.
Topics: Cell Division; Cell Cycle; Cell Line; Stem Cells
PubMed: 36313807
DOI: 10.1016/j.crmeth.2022.100315 -
Cells Jan 2022Cell division and cell cycle mechanism has been studied for 70 years. This research has revealed that the cell cycle is regulated by many factors, including cyclins and... (Review)
Review
Cell division and cell cycle mechanism has been studied for 70 years. This research has revealed that the cell cycle is regulated by many factors, including cyclins and cyclin-dependent kinases (CDKs). Heat shock transcription factors (HSFs) have been noted as critical proteins for cell survival against various stresses; however, recent studies suggest that HSFs also have important roles in cell cycle regulation-independent cell-protective functions. During cell cycle progression, HSF1, and HSF2 bind to condensed chromatin to provide immediate precise gene expression after cell division. This review focuses on the function of these HSFs in cell cycle progression, cell cycle arrest, gene bookmarking, mitosis and meiosis.
Topics: Animals; Cell Cycle; Cell Cycle Checkpoints; Heat Shock Transcription Factors; Humans; Meiosis; Proteolysis
PubMed: 35053319
DOI: 10.3390/cells11020203 -
Cellular & Molecular Biology Letters Apr 2022Autophagy plays an essential role in maintaining cellular homeostasis and in the response to cellular stress. Autophagy is also involved in cell cycle progression, yet...
BACKGROUND
Autophagy plays an essential role in maintaining cellular homeostasis and in the response to cellular stress. Autophagy is also involved in cell cycle progression, yet the relationship between these processes is not clearly defined.
RESULTS
In exploring this relationship, we observed that the inhibition of autophagy impaired the G2/M phase-arresting activity of etoposide but enhanced the G1 phase-arresting activity of palbociclib. We further investigated the connection of basal autophagy and cell cycle by utilizing the autophagosome tracer dye Cyto-ID in two ways. First, we established a double-labeling flow-cytometric procedure with Cyto-ID and the DNA probe DRAQ5, permitting the cell cycle phase-specific determination of autophagy in live cells. This approach demonstrated that different cell cycle phases were associated with different autophagy levels: G1-phase cells had the lowest level, and G2/M-phase cells had the highest one. Second, we developed a flow-cytometric cell-sorting procedure based on Cyto-ID that separates cell populations into fractions with low, medium, and high autophagy. Cell cycle analysis of Cyto-ID-sorted cells confirmed that the high-autophagy fraction contained a much higher percentage of G2/M-phase cells than the low-autophagy fraction. In addition, Cyto-ID-based cell sorting also proved to be useful for assessing other autophagy-related processes: extracellular flux analysis revealed metabolic differences between the cell populations, with higher autophagy being associated with higher respiration, higher mitochondrial ATP production, and higher glycolysis.
CONCLUSION
This work provides clear evidence of high autophagy in G2/M-phase cells by establishing a novel cell sorting technique based on Cyto-ID.
Topics: Autophagy; Cell Cycle; Cell Division; G1 Phase; Humans; Leukemia
PubMed: 35382734
DOI: 10.1186/s11658-022-00334-8 -
Genes Jul 2023D-type cyclins encode G1/S cell cycle checkpoint proteins, which play a crucial role in defining cell cycle exit and progression. Precise control of cell cycle exit is... (Review)
Review
D-type cyclins encode G1/S cell cycle checkpoint proteins, which play a crucial role in defining cell cycle exit and progression. Precise control of cell cycle exit is vital during embryonic development, with defects in the pathways regulating intracellular D-type cyclins resulting in abnormal initiation of stem cell differentiation in a variety of different organ systems. Furthermore, stabilisation of D-type cyclins is observed in a wide range of disorders characterized by cellular over-proliferation, including cancers and overgrowth disorders. In this review, we will summarize and compare the roles played by each D-type cyclin during development and provide examples of how their intracellular dysregulation can be an underlying cause of disease.
Topics: Cyclins; Cyclin D3; Cell Division; Cell Cycle; Cell Proliferation
PubMed: 37510349
DOI: 10.3390/genes14071445 -
Cell Proliferation Jun 2003Apoptosis and proliferation are intimately coupled. Some cell cycle regulators can influence both cell division and programmed cell death. The linkage of cell cycle and... (Review)
Review
Apoptosis and proliferation are intimately coupled. Some cell cycle regulators can influence both cell division and programmed cell death. The linkage of cell cycle and apoptosis has been recognized for c-Myc, p53, pRb, Ras, PKA, PKC, Bcl-2, NF-kappa B, CDK, cyclins and CKI. This review summarizes the different functions of the proteins presently known to control both apoptosis and cell cycle progression. These proteins can influence apoptosis or proliferation but different variables, including cell type, cellular environment and genetic background, make it difficult to predict the outcome of cell proliferation, cell cycle arrest or cell death. These important decisions of cell proliferation or cell death are likely to be controlled by more than one signal and are necessary to ensure a proper cellular response.
Topics: Animals; Apoptosis; Cell Cycle; Cell Cycle Proteins; Cell Division; Cyclins; Humans; Models, Biological; Oncogenes; Phosphotransferases
PubMed: 12814432
DOI: 10.1046/j.1365-2184.2003.00267.x -
Cell Cycle (Georgetown, Tex.) 2014
Topics: Cell Cycle; Epigenomics; Humans; RNA, Long Noncoding
PubMed: 25485487
DOI: 10.4161/15384101.2014.962860 -
International Journal of Molecular... Jul 2022Production of new cells as a result of progression through the cell division cycle is a fundamental biological process for the perpetuation of both unicellular and... (Review)
Review
Production of new cells as a result of progression through the cell division cycle is a fundamental biological process for the perpetuation of both unicellular and multicellular organisms. In the case of plants, their developmental strategies and their largely sessile nature has imposed a series of evolutionary trends. Studies of the plant cell division cycle began with cytological and physiological approaches in the 1950s and 1960s. The decade of 1990 marked a turn point with the increasing development of novel cellular and molecular protocols combined with advances in genetics and, later, genomics, leading to an exponential growth of the field. In this article, I review the current status of plant cell cycle studies but also discuss early studies and the relevance of a multidisciplinary background as a source of innovative questions and answers. In addition to advances in a deeper understanding of the plant cell cycle machinery, current studies focus on the intimate interaction of cell cycle components with almost every aspect of plant biology.
Topics: Cell Cycle; Cell Division; Plant Cells; Plants
PubMed: 35897730
DOI: 10.3390/ijms23158154 -
Annals of Botany Oct 2017Quiescence is a fundamental feature of plant life, which enables plasticity, renewal and fidelity of the somatic cell line. Cellular quiescence is defined by arrest in a... (Review)
Review
BACKGROUND
Quiescence is a fundamental feature of plant life, which enables plasticity, renewal and fidelity of the somatic cell line. Cellular quiescence is defined by arrest in a particular phase of the cell cycle, typically G1 or G2; however, the regulation of quiescence and proliferation can also be considered across wider scales in space and time. As such, quiescence is a defining feature of plant development and phenology, from meristematic stem cell progenitors to terminally differentiated cells, as well as dormant or suppressed seeds and buds. While the physiology of each of these states differs considerably, each is referred to as 'cell cycle arrest' or 'G1 arrest'.
SCOPE
Here the physiology and molecular regulation of (1) meristematic quiescence, (2) dormancy and (3) terminal differentiation (cell cycle exit) are considered in order to determine whether and how the molecular decisions guiding these nuclear states are distinct. A brief overview of the canonical cell cycle regulators is provided, and the genetic and genomic, as well as physiological, evidence is considered regarding two primary questions: (1) Are the canonical cell cycle regulators superior or subordinate in the regulation of quiescence? (2) Are these three modes of quiescence governed by distinct molecular controls?
CONCLUSION
Meristematic quiescence, dormancy and terminal differentiation are each predominantly characterized by G1 arrest but regulated distinctly, at a level largely superior to the canonical cell cycle. Meristematic quiescence is intrinsically linked to non-cell-autonomous regulation of meristem cell identity, and particularly through the influence of ubiquitin-dependent proteolysis, in partnership with reactive oxygen species, abscisic acid and auxin. The regulation of terminal differentiation shares analogous features with meristematic quiescence, albeit with specific activators and a greater role for cytokinin signalling. Dormancy meanwhile appears to be regulated at the level of chromatin accessibility, by Polycomb group-type histone modifications of particular dormancy genes.
Topics: Cell Cycle Checkpoints; G1 Phase; Meristem; Plant Development; Plant Dormancy; Plant Roots; Plant Shoots; Plants; Resting Phase, Cell Cycle; S Phase
PubMed: 28981580
DOI: 10.1093/aob/mcx082 -
Cytometry. Part a : the Journal of the... Aug 2020Cell cycle analysis by mass cytometry (MC) is hampered by the poor resolution of the Iridium-labeled DNA intercalator compared to DNA-specific fluorescent dyes. We...
Cell cycle analysis by mass cytometry (MC) is hampered by the poor resolution of the Iridium-labeled DNA intercalator compared to DNA-specific fluorescent dyes. We report here a minimum cell cycle panel for MC consisting of Ir-intercalator (DNA content), IdU (S phase), anti-pS28HistoneH3 (mitosis), anti-CDT1 (G phase) and anti-Geminin (non-G phases). Cell cycle distributions obtained by MC were not significantly different from fluorescence flow cytometry results (r = 0.98, P < 0.001). Further subdivision of the G and G phases could be done with anti-pS780RB1 (late G ) and anti-PLK1 (late G ), respectively. A disadvantage of MC is that aggregates of cells cannot easily be removed while retaining all single cells. We have developed an analysis pipeline including unsupervised clustering by FlowSOM and subsequent single-cell gating. When performed on cells stained with the cell cycle panel, this analysis pipeline successfully identified debris, dead/apoptotic cells, nonsingle-cell populations and the major cell cycle phases. The presented cell cycle panel and analysis pipeline thus achieves true single-cell analysis at the same time as any additional channels in the panel are open for phenotyping and cell cycle-resolved expression or modification analysis. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals LLC. on behalf of International Society for Advancement of Cytometry.
Topics: Cell Cycle; Cluster Analysis; Flow Cytometry; Humans; Mitosis; S Phase
PubMed: 31943748
DOI: 10.1002/cyto.a.23960