scholarly journals THE LOSS OF PHENOTYPIC TRAITS BY DIFFERENTIATED CELLS

1969 ◽  
Vol 130 (2) ◽  
pp. 417-442 ◽  
Author(s):  
S. Chacko ◽  
J. Abbott ◽  
S. Holtzer ◽  
H. Holtzer
Keyword(s):  
Cell Surface ◽  
Chondroitin Sulfate ◽  
Phenotypic Traits ◽  
Differentiated Cells ◽  
Chondrogenic Phenotype ◽  
History Of ◽  
A Cell ◽  
Fibroblastic Cells ◽  
Cell Cell

A single, functional, mitotically quiescent chondrocyte may be induced to reenter the mitotic cyde, and produce a progeny of over 1011 cells. Sessile, adherent, polygonal cells deposit matrix, whereas amoeboid, dispersed, flattened fibroblastic cells do not. The prior synthetic history of a cell is of greater importance in determining whether the characteristic chondrogenic phenotype will be expressed, rather than growth in "permissive" or "nonpermissive" medium. Clonal conditions select for stem-like cells, some of whose progeny may become polygonal chondrocytes. The retention of the characteristic chondrogenic phenotype in vitro is favored by pruning the dedifferentiated chondrocytes which arise in these cultures. Dedifferentiated chondrocytes interfere with the deposition and synthesis of chondroitin sulfate by neighboring functional chondrocytes. Possible mechanisms are proposed to explain this type of cell-cell or cell exudate interference. If the progeny of a single, genetically programmed chondrocyte may or may not synthesize chondroitin sulfate, then extragenic sites in the cytoplasm or cell surface must influence the decision as to which cluster of "luxur" molecules the cell will synthesize.

scholarly journals THE LOSS OF PHENOTYPIC TRAITS BY DIFFERENTIATED CELLS

1966 ◽  
Vol 28 (3) ◽  
pp. 473-487 ◽  
Author(s):  
Joan Abbott ◽  
Howard Holtzer
Keyword(s):  
Dna Synthesis ◽  
Chondroitin Sulfate ◽  
Collagen Synthesis ◽  
Dna Interaction ◽  
Cell Multiplication ◽  
Phenotypic Traits ◽  
Embryonic Chick ◽  
Differentiated Cells ◽  
Genetically Determined

Observations were made on the behavior of chondrocytes grown under various conditions in vitro. The chondrocytes in 10-day embryonic chick vertebrae were grown as cultures of intact vertebrae, as pellets of chondrocytes liberated from their matrix, and as monodispersed cells plated out on plasma clots. Cartilage matrix was stained metachromatically with toluidine blue. Radioautographs were made of incorporated H3-thymidine, H3-proline, and S35-sulfate to determine the extent of DNA synthesis, collagen synthesis, and chondroitin sulfate synthesis, respectively. Chondrocytes in intact vertebrae or in pellets are rounded and actively synthesizing chondroitin sulfate and collagen. There is little DNA synthesis by cells in either vertebrae or pellets. Chondrocytes grown as monodisperse cells rapidly cease synthesizing cytologically detectable chondroitin sulfate and are induced to synthesize DNA and divide. There is a change in the shape of these chondrocytes from a rounded to a more stellate condition which accompanies the shift in metabolic activity. Conversely, when the cells attain a certain cell density, they reacquire a rounded shape, cease dividing, and again synthesize chondroitin sulfate. Clusters of chondrocytes synthesize more chondroitin sulfate than isolated chondrocytes. It is concluded that most chondrocytes synthesizing chondroitin sulfate do not concurrently synthesize DNA. Interaction between associated chondrocytes is important in inducing and maintaining chondroitin sulfate synthesis in genetically determined chondrocytes. Failure of interaction between chondrocytes leads to DNA synthesis and cell multiplication.

Factors Controlling Electropermeabilisation of Cell Membranes

2002 ◽  
Vol 1 (5) ◽  
pp. 319-327 ◽  
Author(s):  
M. P. Rols ◽  
M. Golzio ◽  
B. Gabriel ◽  
J. Teissié
Keyword(s):  
Cell Surface ◽  
Electric Field ◽  
Pulse Duration ◽  
Cell Membranes ◽  
Physical Parameters ◽  
Local Exchange ◽  
Physical Mechanisms ◽  
A Cell

Electric field pulses are a new approach for drug and gene delivery for cancer therapy. They induce a localized structural alteration of cell membranes. The associated physical mechanisms are well explained and can be safely controlled. A position dependent modulation of the membrane potential difference is induced when an electric field is applied to a cell. Electric field pulses with an overcritical intensity evoke a local membrane alteration. A free exchange of hydrophilic low molecular weight molecules takes place across the membrane. A leakage of cytosolic metabolites and a loading of polar drugs into the cytoplasm are obtained. The fraction of the cell surface which is competent for exchange is a function of the field intensity. The level of local exchange is strongly controlled by the pulse duration and the number of successive pulses. The permeabilised state is long lived. Its lifetime is under the control of the cumulated pulse duration. Cell viability can be preserved. Gene transfer is obtained but its mechanism is not a free diffusion. Plasmids are electrophoretically accumulated against the permeabilised cell surface and form aggregates due to the field effect. After the pulses, several steps follow: translocation to the cytoplasm, traffic to the nucleus and expression. Molecular structural and metabolic changes in cells remain mostly poorly understood. Nevertheless, while most studies were established on cells in culture ( in vitro), recent experiments show that similar effects are obtained on tissue ( in vivo). Transfer remains controlled by the physical parameters of the electrical treatment.

scholarly journals Ephrin-B3 controls excitatory synapse density through cell-cell competition for EphBs

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Nathan T Henderson ◽  
Sylvain J Le Marchand ◽  
Martin Hruska ◽  
Simon Hippenmeyer ◽  
Liqun Luo ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Spine Density ◽  
Cell Competition ◽  
Intrinsic Factors ◽  
Genetic Mouse Model ◽  
Synapse Density ◽  
A Cell ◽  
Cell Cell

Cortical networks are characterized by sparse connectivity, with synapses found at only a subset of axo-dendritic contacts. Yet within these networks, neurons can exhibit high connection probabilities, suggesting that cell-intrinsic factors, not proximity, determine connectivity. Here, we identify ephrin-B3 (eB3) as a factor that determines synapse density by mediating a cell-cell competition that requires ephrin-B-EphB signaling. In a microisland culture system designed to isolate cell-cell competition, we find that eB3 determines winning and losing neurons in a contest for synapses. In a Mosaic Analysis with Double Markers (MADM) genetic mouse model system in vivo the relative levels of eB3 control spine density in layer 5 and 6 neurons. MADM cortical neurons in vitro reveal that eB3 controls synapse density independently of action potential-driven activity. Our findings illustrate a new class of competitive mechanism mediated by trans-synaptic organizing proteins which control the number of synapses neurons receive relative to neighboring neurons.

scholarly journals A generic cell surface ligand system for studying cell-cell recognition

2019 ◽  
Author(s):  
Eleanor M Denham ◽  
Michael I Barton ◽  
Susannah M Black ◽  
Marcus J Bridge ◽  
Ben de Wet ◽  
...  
Keyword(s):  
Cell Surface ◽  
Surface Density ◽  
Cell Receptor ◽  
Surface Receptors ◽  
Ligand System ◽  
Ligand Interactions ◽  
A Cell ◽  
Surface Ligand ◽  
Receptor Biology ◽  
Cell Cell

AbstractDose-response experiments are a mainstay of receptor biology studies and can reveal valuable insights into receptor function. Such studies of receptors that bind cell surface ligands are currently limited by the difficulty in manipulating the surface density of ligands at a cell-cell interface. Here we describe a generic cell surface ligand system that allows precise manipulation of cell surface ligand densities over several orders of magnitude. We validate the system for a range of immunoreceptors, including the T cell receptor (TCR), and show that this generic ligand stimulates via the TCR at a similar surface density as its native ligand. This system allows the effect of surface density, valency, dimensions, and affinity of the ligand to be manipulated. It can be readily extended to other receptor-cell surface ligand interactions, and will facilitate investigation into the activation of, and signal integration between, cell surface receptors.

The putative sponge aggregation receptor. Isolation and characterization of a molecule composed of scavenger receptor cysteine-rich domains and short consensus repeats

1998 ◽  
Vol 111 (17) ◽  
pp. 2635-2644 ◽  
Author(s):  
B. Blumbach ◽  
Z. Pancer ◽  
B. Diehl-Seifert ◽  
R. Steffen ◽  
J. Munkner ◽  
...  
Keyword(s):  
Cell Surface ◽  
Scavenger Receptor ◽  
Cell Surface Receptor ◽  
Functional Assay ◽  
Cdna Clones ◽  
The Third ◽  
Short Consensus Repeats ◽  
Isolation And Characterization ◽  
A Cell ◽  
Cell Cell

Porifera (sponges) are the oldest extant metazoan phylum. Dissociated sponge cells serve as a classic system to study processes of cell reaggregation. The reaggregation of dissociated cells is mediated by an extracellularly localized aggregation factor (AF), based on heterophilic interactions of the third order; the AF bridges two cells by ligating a cell-surface-bound aggregation receptor (AR). In the present study we report cloning, expression and immunohistochemical localization of a polypeptide from the marine sponge Geodia cydonium, which very likely represents the AR. The presumed AR gene gives rise to at least three forms of alternatively spliced transcripts of 6.5, 4.9 and 3.9 kb, as detected by northern blotting. Two cDNA clones corresponding to the shorter forms were already reported earlier; here we present an analysis of the largest. All three putative polypeptides feature scavenger receptor cysteine-rich (SRCR) domains. The largest form, SRCR-SCR-Car, is a cell-surface receptor of molecular mass 220 kDa, which is assumed to be the cell-adhesion receptor AR; the second form, SRCR-Re, is also a putative receptor of 166 kDa, while the third form, SRCR-Mo, is a soluble molecule of 129 kDa. The SRCR-SCR-Car molecule consists of fourteen SRCR domains, six short consensus repeats (SCRs), a C-terminal transmembrane domain and a cytoplasmic tail; its fourteenth SRCR domain features an Arg-Gly-Asp tripeptide. To obtain monoclonal antibodies, a 170-amino-acid-long polypeptide that is found in all three forms of the SRCR-containing proteins was expressed in E. coli. In a western blot of sponge cells lysate the monoclonal antibody raised against the recombinant polypeptide recognized two major immuno-reacting polypeptides (220 and 117 kDa) and two minor bands (36 and 32 kDa). The antibody was found to react with antigen(s) predominantly localized on the plasma membranes of cells, especially those of spherulous cells. In a functional assay Fab' fragments of the antibodies suppressed AF-mediated cell-cell reaggregation. Additionally, a recombinant SRCR-soluble fragment effectively inhibited AF-mediated cell-cell reaggregation. We conclude that the 220 kDa SRCR-containing protein of the sponge G. cydonium is very likely the AR.

Telomerase and immortalization

2019 ◽  
pp. 209-220
Author(s):  
Laura Collopy ◽  
Kazunori Tomita
Keyword(s):  
Cell Cycle ◽  
Growth And Development ◽  
Normal Cell ◽  
Chromosome Instability ◽  
Growth Arrest ◽  
Proliferative Capacity ◽  
Differentiated Cells ◽  
Dividing Cells ◽  
History Of ◽  
A Cell

The lifetime of a cell is set by the terminal ends of our chromosomes, ageing timers called telomeres. Most dividing cells, not exceptional for cancers, require telomeres to protect chromosomes. However, telomere erosion occurs at every cell cycle, thus imposing a proliferative capacity, eventually triggering a growth arrest. Cancer cells must overcome this proliferative limit in order to continue dividing. In the vast majority of cases, the growth and progression of cancers correlates with the upregulation of telomerase, an enzyme that replenishes telomeres. Telomerase is not active in normal, differentiated cells and its reactivation in cancer renders cells immortal and promotes their continued growth and development. Curiously, in cancer telomerase maintains short telomeres, retaining chromosome instability. Here, we briefly take you through history of cellular mortality with the connection to telomeres and telomerase and review their function in the normal cell to address their role during the transformation to malignancy.

scholarly journals PTP1B Modulates the Association of β-Catenin with N-cadherin through Binding to an Adjacent and Partially Overlapping Target Site

2002 ◽  
Vol 277 (51) ◽  
pp. 49989-49997 ◽  
Author(s):  
Gang Xu ◽  
Carlos Arregui ◽  
Jack Lilien ◽  
Janne Balsamo
Keyword(s):  
Amino Acids ◽  
Cell Surface ◽  
Tyrosine Phosphatase ◽  
Target Site ◽  
Target Domain ◽  
Chick Retina ◽  
Cell Permeable Peptide ◽  
A Cell ◽  
Relationship Of

The nonreceptor tyrosine phosphatase PTP1B associates with the cytoplasmic domain of N-cadherin and may regulate cadherin function through dephosphorylation of β-catenin. We have now identified the domain on N-cadherin to which PTP1B binds and characterized the effect of perturbing this domain on cadherin function. Deletion constructs lacking amino acids 872–891 fail to bind PTP1B. This domain partially overlaps with the β-catenin binding domain. To further define the relationship of these two sites, we used peptides to competein vitrobinding. A peptide representing the most NH2-terminal 8 amino acids of the PTP1B binding site, the region of overlap with the β-catenin target, effectively competes for binding of β-catenin but is much less effective in competing PTP1B, whereas two peptides representing the remaining 12 amino acids have no effect on β-catenin binding but effectively compete for PTP1B binding. Introduction into embryonic chick retina cells of a cell-permeable peptide mimicking the 8 most COOH-terminal amino acids in the PTP1B target domain, the region most distant from the β-catenin target site, prevents binding of PTP1B, increases the pool of free, tyrosine-phosphorylated β-catenin, and results in loss of N-cadherin function. N-cadherin lacking this same region of the PTP1B target site does not associate with PTP1B or β-catenin and is not efficiently expressed at the cell surface of transfected L cells. Thus, interaction of PTP1B with N-cadherin is essential for its association with β-catenin, stable expression at the cell surface, and consequently, cadherin function.

scholarly journals Cytotoxicity of a cell-reactive immunotoxin containing ricin A chain is potentiated by an anti-immunotoxin containing ricin B chain.

1984 ◽  
Vol 160 (1) ◽  
pp. 341-346 ◽  
Author(s):  
E S Vitetta ◽  
R J Fulton ◽  
J W Uhr
Keyword(s):  
Cell Surface ◽  
Cell Line ◽  
Ricin A Chain ◽  
Daudi Cell ◽  
A Cell ◽  
A Chain ◽  
Ricin A

In vitro killing of the human Daudi cell line by either univalent [F(ab')] or divalent (IgG) forms of rabbit anti-human Ig (RAHIg) coupled to ricin A chain can be specifically potentiated by a "piggyback" treatment with ricin B chain coupled to goat anti-rabbit Ig (GARIg). When cells are treated with univalent immunotoxin (IT) [F(ab') RAHIg-A] and then cultured, IT can be detected on the cell surface for at least 5 h, since GARIg-B can still enhance killing at this time. These results provide a strategy for in vivo use of A chain- and B chain-containing IT.

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