scholarly journals Primary Cilium Disassembly in Mammalian Cells Occurs Predominantly by Whole-Cilium Shedding

2018 ◽  
Author(s):  
Mary Mirvis ◽  
Kathleen Siemers ◽  
W. James Nelson ◽  
Tim Stearns
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Primary Cilium ◽  
Mammalian Cells ◽  
Live Cell Imaging ◽  
Culture Medium ◽  
Cell Imaging ◽  
Animal Cells ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

AbstractThe primary cilium is a central signaling hub in cell proliferation and differentiation, and is built and disassembled every cell cycle in most animal cells. Disassembly is critically important: misregulation or delay of disassembly leads to cell cycle defects. The physical means by which cilia are disassembled are poorly understood, and thought to involve resorption of disassembled components into the cell body. To investigate cilium disassembly in mammalian cells, we used rapid live-cell imaging to comprehensively characterize individual disassembly events. The predominant mode of disassembly was rapid cilium loss via deciliation, in which the membrane and axoneme of the cilium was shed from the cell. Gradual resorption was also observed, as well as events in which a period of gradual resorption ended with rapid deciliation. Deciliation resulted in intact shed cilia that could be recovered from culture medium and contained both membrane and axoneme proteins. We modulated levels of katanin and intracellular calcium, two putative regulators of deciliation, and found that excess katanin promotes disassembly by deciliation, independently of calcium. Together, these results demonstrate that mammalian ciliary disassembly involves a tunable decision between deciliation and resorption.

scholarly journals MicroRNA let-7b regulates neural stem cell proliferation and differentiation by targeting nuclear receptor TLX signaling

2010 ◽  
Vol 107 (5) ◽  
pp. 1876-1881 ◽  
Author(s):  
Chunnian Zhao ◽  
GuoQiang Sun ◽  
Shengxiu Li ◽  
Ming-Fei Lang ◽  
Su Yang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Cyclin D1 ◽  
Neural Stem Cell ◽  
Neural Differentiation ◽  
Stem Cell Proliferation ◽  
Neural Stem Cell Proliferation ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

Neural stem cell self-renewal and differentiation is orchestrated by precise control of gene expression involving nuclear receptor TLX. Let-7b, a member of the let-7 microRNA family, is expressed in mammalian brains and exhibits increased expression during neural differentiation. However, the role of let-7b in neural stem cell proliferation and differentiation remains unknown. Here we show that let-7b regulates neural stem cell proliferation and differentiation by targeting the stem cell regulator TLX and the cell cycle regulator cyclin D1. Overexpression of let-7b led to reduced neural stem cell proliferation and increased neural differentiation, whereas antisense knockdown of let-7b resulted in enhanced proliferation of neural stem cells. Moreover, in utero electroporation of let-7b to embryonic mouse brains led to reduced cell cycle progression in neural stem cells. Introducing an expression vector of Tlx or cyclin D1 that lacks the let-7b recognition site rescued let-7b-induced proliferation deficiency, suggesting that both TLX and cyclin D1 are important targets for let-7b-mediated regulation of neural stem cell proliferation. Let-7b, by targeting TLX and cyclin D1, establishes an efficient strategy to control neural stem cell proliferation and differentiation.

scholarly journals Cell cycle-dependent phosphorylation and regulation of cellular differentiation

2018 ◽  
Vol 46 (5) ◽  
pp. 1083-1091 ◽  
Author(s):  
Laura J.A. Hardwick ◽  
Roberta Azzarelli ◽  
Anna Philpott
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Diverse Range ◽  
Cyclin Dependent Kinases ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Stem And Progenitor Cells ◽  
Cycle Dependent ◽  
Cell Cycle Dynamics ◽  
Bidirectional Interactions

Embryogenesis requires an exquisite regulation of cell proliferation, cell cycle withdrawal and differentiation into a massively diverse range of cells at the correct time and place. Stem cells also remain to varying extents in different adult tissues, acting in tissue homeostasis and repair. Therefore, regulated proliferation and subsequent differentiation of stem and progenitor cells remains pivotal throughout life. Recent advances have characterised the cell cycle dynamics, epigenetics, transcriptome and proteome accompanying the transition from proliferation to differentiation, revealing multiple bidirectional interactions between the cell cycle machinery and factors driving differentiation. Here, we focus on a direct mechanistic link involving phosphorylation of differentiation-associated transcription factors by cell cycle-associated Cyclin-dependent kinases. We discuss examples from the three embryonic germ layers to illustrate this regulatory mechanism that co-ordinates the balance between cell proliferation and differentiation.

scholarly journals PPARs Expression in Adult Mouse Neural Stem Cells: Modulation of PPARs during Astroglial Differentiaton of NSC

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-10 ◽  
Author(s):  
A. Cimini ◽  
L. Cristiano ◽  
E. Benedetti ◽  
B. D'Angelo ◽  
M. P. Cerù
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Transcription Factors ◽  
Neural Stem Cells ◽  
Osteoblast Differentiation ◽  
Adult Mouse ◽  
Cell Type ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

PPAR isotypes are involved in the regulation of cell proliferation, death, and differentiation, with different roles and mechanisms depending on the specific isotype and ligand and on the differentiated, undifferentiated, or transformed status of the cell. Differentiation stimuli are integrated by key transcription factors which regulate specific sets of specialized genes to allow proliferative cells to exit the cell cycle and acquire specialized functions. The main differentiation programs known to be controlled by PPARs both during development and in the adult are placental differentiation, adipogenesis, osteoblast differentiation, skin differentiation, and gut differentiation. PPARs may also be involved in the differentiation of macrophages, brain, and breast. However, their functions in this cell type and organs still awaits further elucidation. PPARs may be involved in cell proliferation and differentiation processes of neural stem cells (NSC). To this aim, in this work the expression of the three PPAR isotypes and RXRs in NSC has been investigated.

scholarly journals Use of a double-label method to detect rapid changes in the rate of cell proliferation.

1992 ◽  
Vol 40 (5) ◽  
pp. 619-627 ◽  
Author(s):  
G A Hyatt ◽  
D C Beebe
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Short Pulse ◽  
S Phase ◽  
Fiber Cells ◽  
Label Method ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Double Label ◽  
Lens Cell

We developed a double-label method to directly measure the rate at which cells enter S-phase of the cell cycle. All cells in S-phase were first labeled with a short pulse of [3H]-thymidine. This was followed by a longer incubation in bromodeoxyuridine (BrdU), a thymidine analogue. Nuclei labeled with [3H]-thymidine were detected by autoradiography and those labeled with BrdU by immunocytochemistry. Cells labeled only with BrdU must have entered S-phase at some time after the end of the [3H]-thymidine pulse. Thus, the rate of entry of cells into S-phase could be determined. This method was shown to be more accurate and more sensitive than determining changes in the rate at which cells entered S-phase with a continuous labeling protocol. It was possible to detect changes in proliferative activity that occurred in less than 1 hr. We used this double-label technique to study changes in the cell cycle during the terminal differentiation of chicken embryo lens fiber cells. These studies revealed differences in the effects of several treatments known to stimulate fiber cell differentiation. They also demonstrated the presence in the embryonic eye of factors that stimulate and prevent lens cell proliferation and differentiation.

Depletion in nuclear spermine during human spermatogenesis, a natural process of cell differentiation

1992 ◽  
Vol 263 (2) ◽  
pp. C343-C347 ◽  
Author(s):  
V. Quemener ◽  
Y. Blanchard ◽  
D. Lescoat ◽  
R. Havouis ◽  
J. P. Moulinoux
Keyword(s):  
Cell Proliferation ◽  
Cell Differentiation ◽  
Mammalian Cells ◽  
Gradient Centrifugation ◽  
Cell Nuclei ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Human Spermatogenesis

Polyamines (PA), polycations present in all mammalian cells, are essential for cell proliferation and differentiation. In vitro, PA are known to bind to DNA with a high affinity. In vivo, the intimate association of endogenous PA with highly condensed chromatin has been reported. During spermatogenesis, when processes of cell proliferation and differentiation take place, the potential role of polyamines has not been studied in depth. We report here the PA levels measured in human spermatogenic cell nuclei at different stages of differentiation. Cell populations (spermatocytes and round, elongating, or elongated spermatids) were obtained after submitting human testes to a trypsin-deoxyribonuclease digestion, then to a centrifugal elutriation and Percoll gradient centrifugation. A significant and progressive nuclear spermine level decrease was observed from primary spermatocytes to elongated spermatids. This release of spermine from nuclei was concomitant with three major events in mammalian spermiogenesis: the reduction of DNA transcription activity, the replacement of histone proteins by protamines, and the compaction of chromatin. This is the first report arguing a release of nuclear spermine during an in vivo physiological cell differentiation process.

Protein kinase C involvement in cell cycle modulation

2014 ◽  
Vol 42 (5) ◽  
pp. 1471-1476 ◽  
Author(s):  
Alessandro Poli ◽  
Sara Mongiorgi ◽  
Lucio Cocco ◽  
Matilde Y. Follo
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Cell Models ◽  
Cycle Progression ◽  
Cyclin Dependent Kinases ◽  
Kinase C ◽  
Cell Proliferation And Differentiation ◽  
Cell Cycle Modulation ◽  
Proliferation And Differentiation

Protein kinases C (PKCs) are a family of serine/threonine kinases which act as key regulators in cell cycle progression and differentiation. Studies of the involvement of PKCs in cell proliferation showed that their role is dependent on cell models, cell cycle phases, timing of activation and localization. Indeed, PKCs can positively and negatively act on it, regulating entry, progression and exit from the cell cycle. In particular, the targets of PKCs resulted to be some of the key proteins involved in the cell cycle including cyclins, cyclin-dependent kinases (Cdks), Cip/Kip inhibitors and lamins. Several findings described roles for PKCs in the regulation of G1/S and G2/M checkpoints. As a matter of fact, data from independent laboratories demonstrated PKC-related modulations of cyclins D, leading to effects on the G1/S transition and differentiation of different cell lines. Moreover, interesting data were published on PKC-mediated phosphorylation of lamins. In addition, PKC isoenzymes can accumulate in the nuclei, attracted by different stimuli including diacylglycerol (DAG) fluctuations during cell cycle progression, and target lamins, leading to their disassembly at mitosis. In the present paper, we briefly review how PKCs could regulate cell proliferation and differentiation affecting different molecules related to cell cycle progression.

scholarly journals When Yeast Cells Change their Mind: Cell Cycle 'Start' is Reversible under Starvation

2021 ◽  
Author(s):  
Deniz Irvali ◽  
Fabian P. Schlottmann ◽  
Prathibha Muralidhara ◽  
Iliya Nadelson ◽  
N. Ezgi Wood ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Mammalian Cells ◽  
Live Cell Imaging ◽  
Feedback Loop ◽  
Cell Imaging ◽  
Yeast Cells ◽  
Nutrient Depletion ◽  
Restriction Point ◽  
Cell Cycle Inhibitor ◽  
Nutrient Signaling

Eukaryotic cells decide in late G1 whether to commit to another round of genome duplication and division. This point of irreversible cell cycle commitment is a molecular switch termed 'Restriction Point' in mammals and 'Start' in budding yeast. At Start, yeast cells integrate multiple signals such as pheromones, osmolarity, and nutrients. If sufficient nutrients are lacking, cells will not pass Start. However, how the cells respond to nutrient depletion after they have made the Start decision, remains poorly understood. Here, we analyze by live cell imaging how post-Start yeast cells respond to nutrient depletion. We monitor fluorescently labelled Whi5, the cell cycle inhibitor whose export from the nucleus determines Start. Surprisingly, we find that cells that have passed Start can re-import Whi5 back into the nucleus. This occurs when cells are faced with starvation up to 20 minutes after Start. In these cells, the positive feedback loop is interrupted, Whi5 re-binds DNA, and CDK activation occurs a second time once nutrients are replenished. Cells which re-import Whi5 also become sensitive to mating pheromone again, and thus behave like pre-Start cells. In summary, we show that upon starvation the commitment decision at Start can be reversed. We therefore propose that in yeast, as has been suggested for mammalian cells, cell cycle commitment is a multi-step process, where irreversibility in face of nutrient signaling is only reached approximately 20 minutes after CDK activation at Start.

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