scholarly journals Positive Feedback Between PU.1 and the Cell Cycle Controls Myeloid Differentiation

Science ◽  
2013 ◽  
Vol 341 (6146) ◽  
pp. 670-673 ◽  
Author(s):  
Hao Yuan Kueh ◽  
Ameya Champhekar ◽  
Stephen L. Nutt ◽  
Michael B. Elowitz ◽  
Ellen V. Rothenberg
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Positive Feedback ◽  
Regulatory Gene ◽  
Control Cell ◽  
Stem Cell Differentiation ◽  
Myeloid Differentiation ◽  
Cycle Duration ◽  
Gene Circuits ◽  
Cell Cycles

Regulatory gene circuits with positive-feedback loops control stem cell differentiation, but several mechanisms can contribute to positive feedback. Here, we dissect feedback mechanisms through which the transcription factor PU.1 controls lymphoid and myeloid differentiation. Quantitative live-cell imaging revealed that developing B cells decrease PU.1 levels by reducing PU.1 transcription, whereas developing macrophages increase PU.1 levels by lengthening their cell cycles, which causes stable PU.1 accumulation. Exogenous PU.1 expression in progenitors increases endogenous PU.1 levels by inducing cell cycle lengthening, implying positive feedback between a regulatory factor and the cell cycle. Mathematical modeling showed that this cell cycle–coupled feedback architecture effectively stabilizes a slow-dividing differentiated state. These results show that cell cycle duration functions as an integral part of a positive autoregulatory circuit to control cell fate.

scholarly journals Control of tissue development by cell cycle dependent transcriptional filtering

2020 ◽  
Author(s):  
Maria Abou Chakra ◽  
Ruth Isserlin ◽  
Thinh Tran ◽  
Gary D. Bader
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Control Cell ◽  
Cell Types ◽  
Cycle Duration ◽  
Cell Diversity ◽  
Cycle Dependent ◽  
Cell Cycle Dynamics ◽  
Different Cell Types ◽  
Long Genes

AbstractCell cycle duration changes dramatically during development, starting out fast to generate cells quickly and slowing down over time as the organism matures. The cell cycle can also act as a transcriptional filter to control the expression of long genes which are partially transcribed in short cycles. Using mathematical simulations of cell proliferation, we identify an emergent property, that this filter can act as a tuning knob to control cell fate, cell diversity and the number and proportion of different cell types in a tissue. Our predictions are supported by comparison to single-cell RNA-seq data captured over embryonic development. Evolutionary genome analysis shows that fast developing organisms have a narrow genomic distribution of gene lengths while slower developers have an expanded number of long genes. Our results support the idea that cell cycle dynamics may be important across multicellular animals for controlling gene expression and cell fate.

scholarly journals Ran1 functions to control the Cdc10/Sct1 complex through Puc1.

1997 ◽  
Vol 8 (6) ◽  
pp. 1117-1128 ◽  
Author(s):  
M Caligiuri ◽  
T Connolly ◽  
D Beach
Keyword(s):  
Phase Transition ◽  
Cell Cycle ◽  
Protein Kinase ◽  
Cell Fate ◽  
Biochemical Analysis ◽  
Control Cell ◽  
S Phase ◽  
Present Evidence ◽  
Phosphorylation State

We have undertaken a biochemical analysis of the regulation of the G1/S-phase transition and commitment to the cell cycle in the fission yeast Schizosaccharomyces pombe. The execution of Start requires the activity of the Cdc2 protein kinase and the Sct1/Cdc10 transcription complex. Progression through G1 also requires the Ran1 protein kinase whose inactivation leads to activation of the meiotic pathway under conditions normally inhibitory to this process. We have found that in addition to Cdc2, Sct1/Cdc10 complex formation requires Ran1. We demonstrate that the Puc1 cyclin associates with Ran1 and Cdc10 in vivo and that the Ran1 protein kinase functions to control the association between Puc1 and Cdc10. In addition, we present evidence that the phosphorylation state of Cdc10 is altered upon inactivation of Ran1. These results provide biochemical evidence that demonstrate one mechanism by which the Ran1 protein kinase serves to control cell fate through Cdc10 and Puc1.

scholarly journals Co-ordination of cell cycle and differentiation in the developing nervous system

2012 ◽  
Vol 444 (3) ◽  
pp. 375-382 ◽  
Author(s):  
Christopher Hindley ◽  
Anna Philpott
Keyword(s):  
Cell Cycle ◽  
Nervous System ◽  
Embryonic Development ◽  
Cell Fate ◽  
Cell Cycle Progression ◽  
Control Cell ◽  
Cell Cycle Regulators ◽  
Cyclin Dependent Kinases ◽  
Proliferation And Differentiation ◽  
Developing Nervous System

During embryonic development, cells must divide to produce appropriate numbers, but later must exit the cell cycle to allow differentiation. How these processes of proliferation and differentiation are co-ordinated during embryonic development has been poorly understood until recently. However, a number of studies have now given an insight into how the cell cycle machinery, including cyclins, CDKs (cyclin-dependent kinases), CDK inhibitors and other cell cycle regulators directly influence mechanisms that control cell fate and differentiation. Conversely, examples are emerging of transcriptional regulators that are better known for their role in driving the differentiated phenotype, which also play complementary roles in controlling cell cycle progression. The present review will summarise our current understanding of the mechanisms co-ordinating the cell cycle and differentiation in the developing nervous system, where these links have been, perhaps, most extensively studied.

scholarly journals Excess histone H3 is a Chk1 inhibitor that controls embryonic cell cycle progression

2020 ◽  
Author(s):  
Yuki Shindo ◽  
Amanda A. Amodeo
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Cell Cycle Progression ◽  
Histone H3 ◽  
Embryonic Cell ◽  
Cycle Progression ◽  
Cell Cycles ◽  
Embryonic Cell Cycle

AbstractThe early embryos of many species undergo a switch from rapid, reductive cleavage divisions to slower, cell fate-specific division patterns at the Mid-Blastula Transition (MBT). The maternally loaded histone pool is used to measure the increasing ratio of nuclei to cytoplasm (N/C ratio) to control MBT onset, but the molecular mechanism of how histones regulate the cell cycle has remained elusive. Here, we show that excess histone H3 inhibits the DNA damage checkpoint kinase Chk1 to promote cell cycle progression in the Drosophila embryo. We find that excess H3-tail that cannot be incorporated into chromatin is sufficient to shorten the embryonic cell cycle and reduce the activity of Chk1 in vitro and in vivo. Removal of the Chk1 phosphosite in H3 abolishes its ability to regulate the cell cycle. Mathematical modeling quantitatively supports a mechanism where changes in H3 nuclear concentrations over the final cell cycles leading up to the MBT regulate Chk1-dependent cell cycle slowing. We provide a novel mechanism for Chk1 regulation by H3, which is crucial for proper cell cycle remodeling during early embryogenesis.

scholarly journals Hidden long-range memories of growth and cycle speed correlate cell cycles in lineage trees

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Erika E Kuchen ◽  
Nils B Becker ◽  
Nina Claudino ◽  
Thomas Höfer
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Long Range ◽  
Human Cancer ◽  
Embryonic Stem ◽  
Minimum Size ◽  
Cycle Duration ◽  
Correlation Pattern ◽  
Cell Cycles ◽  
Lineage Trees

Cell heterogeneity may be caused by stochastic or deterministic effects. The inheritance of regulators through cell division is a key deterministic force, but identifying inheritance effects in a systematic manner has been challenging. Here, we measure and analyze cell cycles in deep lineage trees of human cancer cells and mouse embryonic stem cells and develop a statistical framework to infer underlying rules of inheritance. The observed long-range intra-generational correlations in cell-cycle duration, up to second cousins, seem paradoxical because ancestral correlations decay rapidly. However, this correlation pattern is naturally explained by the inheritance of both cell size and cell-cycle speed over several generations, provided that cell growth and division are coupled through a minimum-size checkpoint. This model correctly predicts the effects of inhibiting cell growth or cycle progression. In sum, we show how fluctuations of cell cycles across lineage trees help in understanding the coordination of cell growth and division.

Characterization of the unusually rapid cell cycles during rat gastrulation

Development ◽  
1993 ◽  
Vol 117 (3) ◽  
pp. 873-883 ◽  
Author(s):  
A. Mac Auley ◽  
Z. Werb ◽  
P.E. Mirkes
Keyword(s):  
Cell Cycle ◽  
Cycle Time ◽  
Mammalian Cells ◽  
Primitive Streak ◽  
Cycle Duration ◽  
Embryonic Cells ◽  
Cell Cycle Time ◽  
Cell Cycles ◽  
A Cell ◽  
Cycle Regulation

The onset of gastrulation in rodents is associated with the start of differentiation within the embryo proper and a dramatic increase in the rate of growth and proliferation. We have determined the duration of the cell cycle for mesodermal and ectodermal cells of rat embryos during gastrulation (days 8.5 to 9.5 of gestation) using a stathmokinetic analysis. These embryonic cells are the most rapidly dividing mammalian cells yet described. Most cells of the ectoderm and mesoderm had a cell cycle time of 7 to 7.5 hours, but the cells of the primitive streak divided every 3 to 3.5 hours. Total cell cycle time was reduced by shortening S and G2, as well as G1, in contrast to cells later in development, when cell cycle duration is modulated largely by varying the length of G1. In the ectoderm and mesoderm, G1 was 1.5 to 2 hours, S was 3.5 to 4 hours, and G2 was 30 to 40 minutes. G1, S and G2 were shortened even further in the cells of the primitive streak: G1 was less than 30 minutes, S was 2 to 2.75 hours, and G2 was less than 20 minutes. Thus, progress of cells through all phases of the cell cycle is extensively modified during rodent embryogenesis. Specifically, the increased growth rate during gastrulation is associated with radical changes in cell cycle structure and duration. Further, the commitment of cells to become mesoderm and endoderm by entering the primitive streak is associated with expression of a very short cell cycle during transit of the primitive streak, such that developmental decisions determining germ layer fate are reflected in differences in cell cycle regulation.

scholarly journals Surface sensing stimulates cellular differentiation inCaulobacter crescentus

2020 ◽  
Vol 117 (30) ◽  
pp. 17984-17991 ◽  
Author(s):  
Rhett A. Snyder ◽  
Courtney K. Ellison ◽  
Geoffrey B. Severin ◽  
Gregory B. Whitfield ◽  
Christopher M. Waters ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Cellular Differentiation ◽  
Cell Cycle Progression ◽  
Caulobacter Crescentus ◽  
Control Cell ◽  
Chromosome Replication ◽  
Cycle Progression ◽  
Surface Sensing ◽  
Surface Contact

Cellular differentiation is a fundamental strategy used by cells to generate specialized functions at specific stages of development. The bacteriumCaulobacter crescentusemploys a specialized dimorphic life cycle consisting of two differentiated cell types. How environmental cues, including mechanical inputs such as contact with a surface, regulate this cell cycle remain unclear. Here, we find that surface sensing by the physical perturbation of retracting extracellular pilus filaments accelerates cell-cycle progression and cellular differentiation. We show that physical obstruction of dynamic pilus activity by chemical perturbation or by a mutation in the outer-membrane pilus secretin CpaC stimulates early initiation of chromosome replication. In addition, we find that surface contact stimulates cell-cycle progression by demonstrating that surface-stimulated cells initiate early chromosome replication to the same extent as planktonic cells with obstructed pilus activity. Finally, we show that obstruction of pilus retraction stimulates the synthesis of the cell-cycle regulator cyclic diguanylate monophosphate (c-di-GMP) through changes in the activity and localization of two key regulatory histidine kinases that control cell fate and differentiation. Together, these results demonstrate that surface contact and sensing by alterations in pilus activity stimulateC. crescentusto bypass its developmentally programmed temporal delay in cell differentiation to more quickly adapt to a surface-associated lifestyle.

scholarly journals Coordinating cell polarity and cell cycle progression: what can we learn from flies and worms?

Open Biology ◽  
2013 ◽  
Vol 3 (8) ◽  
pp. 130083 ◽  
Author(s):  
Anna Noatynska ◽  
Nicolas Tavernier ◽  
Monica Gotta ◽  
Lionel Pintard
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Fate ◽  
Cell Polarity ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Asymmetric Cell Division ◽  
Control Cell ◽  
Model Organisms ◽  
Cycle Progression

Spatio-temporal coordination of events during cell division is crucial for animal development. In recent years, emerging data have strengthened the notion that tight coupling of cell cycle progression and cell polarity in dividing cells is crucial for asymmetric cell division and ultimately for metazoan development. Although it is acknowledged that such coupling exists, the molecular mechanisms linking the cell cycle and cell polarity machineries are still under investigation. Key cell cycle regulators control cell polarity, and thus influence cell fate determination and/or differentiation, whereas some factors involved in cell polarity regulate cell cycle timing and proliferation potential. The scope of this review is to discuss the data linking cell polarity and cell cycle progression, and the importance of such coupling for asymmetric cell division. Because studies in model organisms such as Caenorhabditis elegans and Drosophila melanogaster have started to reveal the molecular mechanisms of this coordination, we will concentrate on these two systems. We review examples of molecular mechanisms suggesting a coupling between cell polarity and cell cycle progression.

scholarly journals Cell Cycle Kinetics and Development of Hydra Attenuata

1974 ◽  
Vol 16 (2) ◽  
pp. 349-358 ◽  
Author(s):  
R. D. CAMPBELL ◽  
C. N. DAVID
Keyword(s):  
Cell Cycle ◽  
Nuclear Dna ◽  
Cell Function ◽  
Control Point ◽  
Interstitial Cells ◽  
Total Cell ◽  
Cycle Duration ◽  
Cell Cycles ◽  
Cell Cycle Duration ◽  
Hydra Attenuata

The cell cycle parameters of interstitial cells in Hydra attenuata have been determined. Interstitial cells were classified according to cluster size in which they occur (1, 2, 4, 8 or 16 cells) and morphology using maceration preparations and histological sections. The lengths of G1, S, G2 and M were determined by standard methods of cell cycle analysis using pulse-chase and continuous labelling with [3H]- and [14C]thymidine. Nuclear DNA contents were measured microfluorimetrically. All classes of interstitial cells proliferate but the cell cycle of large interstitial cells occurring singly or in pairs is longer than that of interstitial cells occurring in clusters of 4, 8 and 16 cells. The S-phase is 11-12 h long and G1 is less than 1 h for all classes of interstitial cells. G2 is 3-4 h long for interstitial cells in clusters of 4, 8 and 16 cells giving these cells a total cell cycle duration of 16-17 h. In contrast, large interstitial cells occurring as singles and in clusters of 2 have G2 durations ranging from 4 to 22 h. Two subpopulations can be discerned among these cells, one having a G1 of about 6 h and a total cell cycle of about 19 h, the other having an average G2 of 14 h and a total cell cycle of about 27 h. The differences in cell cycle duration appear to be associated with interstitial cell function. Cells having a short cell cycle are probably committed to nematocyte differentiation, while large interstitial cells having long and variable cell cycles appear to be undetermined stem cells responsible for proliferating further interstitial cells. The variable length of G2 in these cells suggest it as a possible control point.

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