Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CELL DIFFERENTIATION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources
PubMed2001

Increasing the intra-Golgi pH of cultured LS174T goblet-differentiated cells mimics the decreased mucin sulfation and increased Thomsen-Friedenreich antigen (Gal beta1-3GalNac alpha-) expression seen in colon cancer.

Mucins in ulcerative colitis and colon cancer share common properties of reduced sulfation and increased oncofetal carbohydrate antigen expression. It has previously been shown that there is no simple correlation between these changes and the activity of the relevant glycosyl-, sialyl-, and sulfo-transferases. We examined mucin sulfation and expression of oncofetal Thomsen-Friedenreich (TF) antigen (galactosyl beta1-3N-acetylgalactosamine alpha-) in the goblet cell-differentiated human colon cancer cell line LS174T following treatment with bafilomycin A(1, )which raises intra-Golgi pH, or monensin, which disrupts medial-trans Golgi transport. Cells were dual-labeled with sodium [(35)S]-sulfate and D-[6-(3)H(N)]-glucosamine hydrochloride, or labeled with L-[U-(14)C]-threonine alone. Mucin was purified using Sepharose CL-4B gel filtration. Mucin sulfo-Lewis(a) and TF antigen expression were assessed using the F2 anti-sulfo-Lewis(a) monoclonal antibody and peanut agglutinin binding respectively. Bafilomycin (0.01 microM; 48 h) reduced total mucin sulfation, expressed relative to incorporation of glucosamine, to 0.50 +/- 0.04 d.p.m. [(35)S]-sulfate per d.p.m. [(3)H]-glucosamine compared to control, 0.84 +/- 0.05 (p < 0.001, n = 16). This was accompanied by 50.3 +/- 8.0% increased expression of TF antigen (p < 0.01) and 50.1 +/- 5.5% decreased expression of sulfo-Lewis(a) (p < 0.01). The reduced sulfate:glucosamine ratio was largely due to increased incorporation of glucosamine into newly synthesized mucin rather than reduction in total sulfate incorporation. In contrast, monensin only reduced total mucin glycosylation at concentrations > 0.1 microM and had no significant effect on mucin sulfation or TF expression. Intra-Golgi alkalinization affects mucin glycosylation, resulting in decreased mucin sulfation and increased expression of TF antigen, changes that mimic those seen in cancerous and premalignant human colonic epithelium.

Anti-Bacterial Agents↗
PubMed1974

The differentiation pathway of T lymphocytes. Evidence for two differentiated cell types.

Two experimental models have been used to study T-cell differentiation. The first, a graft-vs.-host reaction, was induced by injecting thymocytes or cortisone-resistant thymocytes into lethally irradiated allogeneic mice. The second was tumor graft rejection in allogeneic hosts. Ultrastructural studies at various time intervals revealed two differentiated T-cell types. One of these (the "pale" cell) is probably high cytotoxic as measured in the chromium-release assay, the other (the "dark" cell) may be an "amplifier" cell, helping in the differentiation of cytotoxic cells.

Animals↗
PubMed2005

6-[1-(2,6-difluorophenyl)ethyl]pyrimidinones antagonize cell proliferation and induce cell differentiation by inhibiting (a nontelomeric) endogenous reverse transcriptase.

Two 2,6-difluoro-DABO derivatives (MC 1047, 1, and MC 1220, 2, respectively) were tested against endogenous, nontelomeric reverse transcriptase (endo-RT) in human differentiating cell systems to investigate their antiproliferative and cytodifferentiating activity. The two compounds significantly reduced cell proliferation and facilitated the morphological differentiation of cells. These results propose F(2)-DABOs as useful tools in preventive and/or curative therapy to counteract the loss of differentiation in dedifferentiating pathologies and as antiproliferative drugs in tumor therapy.

Antineoplastic Agents↗
PubMed2003

Squamous cell carcinoma cells differentially stimulate NK cell effector functions: the role of IL-18.

Tumor cells stimulate natural killer (NK) cell effector functions, but the regulation of cytokine secretion and cytolysis is incompletely understood. We tested whether oral and pharyngeal squamous cell carcinoma cell lines differentially stimulated NK cell interferon-gamma (IFN-gamma) secretion and cytolysis using a clone of the NK-92-transformed human NK cell line, NK92.35. SCC-4 and SCC-25 cells, but not FaDu or Cal 27 cells, stimulated robust NK92.35 IFN-gamma secretion. All four carcinoma cell lines were lysed by NK92.35 cells. These findings indicate that carcinoma cells differentially stimulate NK cell IFN-gamma secretion and cytolysis. In Transwell experiments, a combination of SCC-4 or SCC-25 cell soluble factors and contact with FaDu cells synergistically stimulated NK92.35 cell IFN-gamma secretion. Stimulatory SCC-4 cells constitutively secreted IL-18, a cytokine that potently augments IFN-gamma secretion by T cells and NK cells. In contrast, poorly stimulatory FaDu cells produced little or no IL-18, but synergized with recombinant IL-18 to stimulate NK92.35 IFN-gamma secretion. mAb to IL-18 or IL-18 receptor diminished SCC-4-stimulated IFN-gamma secretion by NK92.35 cells and by nontransformed NK cells. Thus, IL-18 was necessary for optimal carcinoma stimulation of NK cell IFN-gamma secretion. In vivo, oral and upper aerodigestive tract epithelia and carcinomas produced IL-18, but one squamous cell carcinoma had heterogeneous IL-18 expression. Thus IL-18 production can account for squamous cell carcinoma differential stimulation of NK cell effector functions in vitro and may be important for stimulation of NK cells in vivo.

Carcinoma, Squamous Cell↗
PubMed1989

Adult T cell leukaemia cells are of CD4+ CDw29+ T cell origin and secrete a B cell differentiation factor.

Cells from six cases of adult T cell leukaemia were studied with respect to phenotypical and functional features. All cells were reactive with anti-CD4 and anti-CDw29 monoclonal antibodies (antibody against helper inducer T cells) but were unreactive with anti-CD45R monoclonal antibody (antibody against suppressor inducer T cells). Functionally, these cells secreted a B cell differentiation factor detected by SKW6-CL4 cell differentiation to IgM-producing cells, this secretion being enhanced by culture with recombinant IL-2. Though these results indicate that adult T cell leukaemia cells are of mature helper inducer T cell origin, these cells strongly suppressed PWM-induced B cell differentiation in the absence of CD8+ suppressor effector T cells.

Aged↗
PubMed1995

Induction of cell differentiation potentiates apoptosis triggered by prior exposure to DNA-damaging drugs.

At the end of their life span, differentiated cells die by apoptosis. Subsets of cells also die, in some cell systems, shortly after exposure to differentiating agents. This suggests that early during differentiation the cells may undergo "priming," during which synthesis and/or activation and accumulation of effectors of apoptosis occurs. The objective of the present study was to test the hypothesis that the signal for apoptosis provided by DNA-damaging drugs given prior to induction of differentiation will be more effective in triggering apoptosis than when given following induction of differentiation. Human promyelocytic HL-60 cells were treated with the topoisomerase I inhibitor camptothecin, the alkylating agent nitrogen mustard, or 5'-azacytidine, an antimetabolite affecting predominantly RNA metabolism. Following drug removal, the cells were postincubated with n-butyrate, which induces differentiation of HL-60 cells along the monocytic pathway, or with all-trans-retinoic acid, which triggers myelocytic differentiation. Multiparameter flow cytometry using two different methods of analysis of apoptosis-associated DNA breakage in situ, as well as evaluation of cell morphology and DNA gel electrophoresis, were used to ascertain the mode of cell death. Increases of 100-200% in the percentage of apoptotic cells were seen when cells were first treated with camptothecin or nitrogen mustard, followed by n-butyrate or retinoic acid, compared to the combined percentage of apoptotic cells when these agents were used individually.(ABSTRACT TRUNCATED AT 250 WORDS)

Antimetabolites, Antineoplastic↗
PubMed2007

Donor cell differentiation, reprogramming, and cloning efficiency: elusive or illusive correlation?

Compared to other assisted reproductive technologies, mammalian nuclear transfer (NT) cloning is inefficient in generating viable offspring. It has been postulated that nuclear reprogramming and cloning efficiency can be increased by choosing less differentiated cell types as nuclear donors. This hypothesis is mainly supported by comparative mouse cloning experiments using early blastomeres, embryonic stem (ES) cells, and terminally differentiated somatic donor cells. We have re-evaluated these comparisons, taking into account different NT procedures, the use of donor cells from different genetic backgrounds, sex, cell cycle stages, and the lack of robust statistical significance when post-blastocyst development is compared. We argue that while the reprogrammability of early blastomeres appears to be much higher than that of somatic cells, it has so far not been conclusively determined whether differentiation status affects cloning efficiency within somatic donor cell lineages.

Animals↗
PubMed2006

Gene expression in TGFbeta-induced epithelial cell differentiation in a three-dimensional intestinal epithelial cell differentiation model.

BACKGROUND: The TGFbeta1-induced signal transduction processes involved in growth and differentiation are only partly known. The three-dimensional epithelial differentiation model, in which T84 epithelial cells are induced to differentiate either with TGFbeta1 or IMR-90 mesenchymal cell-secreted soluble factors, is previously shown to model epithelial cell differentiation seen in intestine. That model has not been used for large scale gene expression studies, such as microarray method. Therefore the gene expression changes were studied in undifferentiated and differentiated three-dimensional T84 cultures with cDNA microarray method in order to study the molecular changes and find new players in epithelial cell differentiation. RESULTS: The expression of 372 genes out of 5188 arrayed sequences was significantly altered, and 47 of them were altered by both mediators. The data were validated and the altered genes are presented in ontology classes. For the genes tested the expressions in protein level were in accordance with the mRNA results. We also found 194 genes with no known function to be potentially important in epithelial cell differentiation. The mRNA expression changes induced by TGFbeta1 were bigger than changes induced by soluble factors secreted by IMR-90 mesenchymal cells. The gene expression data was depicted in already known signaling pathway routes. CONCLUSION: Our results reveal potential new signaling pathways and several new genes affected by TGFbeta in epithelial cell differentiation. The differentiation induced by TGFbeta1 appears to be more potent than the differentiation induced by mesenchymal cells. This study indicates that our cell culture model is a suitable tool in studying regulatory mechanisms during epithelial cell differentiation in intestine. Furthermore the present results indicate that our model is a good tool for finding new players acting in the differentiation of epithelial cells.

Cell Culture Techniques↗
PubMed2000

Hes1 is a negative regulator of inner ear hair cell differentiation.

Hair cell fate determination in the inner ear has been shown to be controlled by specific genes. Recent loss-of-function and gain-of-function experiments have demonstrated that Math1, a mouse homolog of the Drosophila gene atonal, is essential for the production of hair cells. To identify genes that may interact with Math1 and inhibit hair cell differentiation, we have focused on Hes1, a mammalian hairy and enhancer of split homolog, which is a negative regulator of neurogenesis. We report here that targeted deletion of Hes1 leads to formation of supernumerary hair cells in the cochlea and utricle of the inner ear. RT-PCR analysis shows that Hes1 is expressed in inner ear during hair cell differentiation and its expression is maintained in adulthood. In situ hybridization with late embryonic inner ear tissue reveals that Hes1 is expressed in supporting cells, but not hair cells, of the vestibular sensory epithelium. In the cochlea, Hes1 is selectively expressed in the greater epithelial ridge and lesser epithelial ridge regions which are adjacent to inner and outer hair cells. Co-transfection experiments in postnatal rat explant cultures show that overexpression of Hes1 prevents hair cell differentiation induced by Math1. Therefore Hes1 can negatively regulate hair cell differentiation by antagonizing Math1. These results suggest that a balance between Math1 and negative regulators such as Hes1 is crucial for the production of an appropriate number of inner ear hair cells.

Animals↗
PubMed1994

Des (1-3) IGF-I potently enhances differentiated cell growth in olfactory bulb organ culture.

We recently provided evidence that newborn rat olfactory bulb (OB) could be maintained in serum-free organ culture with combinations of insulin-like growth factor-I (IGF-I) and basic fibroblast growth factor (bFGF), both of which are locally synthesized. Des (1-3), or truncated, IGF-I is a potent analog of IGF-I isolated from rat and human brain. We proposed in this study to examine the effects of des (1-3) IGF-I on cell function, morphology and on neuronal and glial cell differentiation in our cultured OB model, using cell-specific immunostains for neurons (150 kDa neurofilament) and glial cells (glial fibrillary associated protein--GFAP). OB were cultured in Iscove's serum-free medium containing IGF-I or des (1-3) IGF-I both alone or in combination with bFGF. Dose dependent responses of 14C amino acid uptake showed des (1-3) IGF-I to be 3-5 fold more potent than IGF-I with a half maximal response at about 20 ng/ml in comparison to 100 ng/ml of IGF-I. The maximum response to IGF-I +/- bFGF was seen at 150 ng/ml; a ten-fold higher dose of insulin +/- bFGF was required to achieve the same response. While morphology was close to fresh 6 day OB following culture with IGF-I (150 ng/ml) and bFGF (25 ng/ml), the substitution of des (1-3) IGF-I at 50 ng/ml markedly improved morphology. Neurons were identified following culture in IGF-I or bFGF alone, but showed greater organisation in the mitral layer following combined IGF-I/bFGF culture. However, in contrast to IGF-I (150 ng/ml), des (1-3) IGF-I (50 ng/ml) supported marked neuronal expression. Furthermore, when des (1-3) IGF-I (50 ng/ml) was substituted for IGF-I, in combination with bFGF, the pattern of enhanced neuronal expression in the mitral layer was very close to that seen in the fresh 6 day bulb, with dendrites projecting to the glomerular layer. In OBs treated with no growth factors, or either IGF-I, des (1-3) IGF-I or bFGF alone, glial expression was widespread and poorly organised, suggesting an injury response. In contrast, following treatment with combinations of bFGF with IGF-I or des (1-3) IGF-I, a more ordered, though enhanced glial response was seen in glomerular and granule cell layers.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2002

Interleukin-13 induces goblet cell differentiation in primary cell culture from Guinea pig tracheal epithelium.

The Th2 cytokines, interleukin (IL)-4 and IL-13, bind to IL-4Ralpha, and cause goblet cell metaplasia/hyperplasia with increased mucin expression in vivo. However, there is not enough evidence that these cytokines directly induce mucin production in vitro. In this study, primary epithelial cells from guinea pig trachea were cultured at an air-liquid interface, and immediately after achieving confluence at Day 7 they were treated with human recombinant IL-4 or IL-13 for 14 d. IL-13-treated cells consisted of a large number of fully mature goblet cells with a smaller number of ciliated cells. Secretory granules of the goblet cells were positive for both periodic acid-Schiff and toluidine blue, and showed exocytosis. By contrast, IL-4 failed to induce goblet cell differentiation. The electric resistances of IL-13-treated cells were lower than those of IL-4-treated cells and nontreated cells, suggesting leaky epithelia. MUC5AC protein level in cell lysates measured by ELISA was several-fold higher in IL-13-treated cells than in nontreated cells, whereas the level in IL-4-treated cells was not changed. These data suggest that human recombinant IL-13, but not IL-4, can induce differentiation into mature goblet cells that produce MUC5AC protein in guinea pig tracheal epithelial cells in vitro.

Animals↗
PubMed2001

Interferon-gamma, tumor necrosis factor-alpha, and transforming growth factor-beta inhibit cyclic AMP-induced Schwann cell differentiation.

Schwann cells differentiate in vivo in response to contact with axons, and cAMP simulates some of these aspects of differentiation in vitro, particularly morphologic changes and expression of certain phenotypic molecules. Unfractionated inflammatory cytokines inhibit cAMP-induced Schwann cell expression of galactolipids (Gal). We sought to identify which cytokines were responsible for this inhibition and to determine whether other phenotypic indicators of Schwann cell differentiation were also affected. Neonatal rat Schwann cells were incubated in vitro with 1 mM 8 Bromo cAMP (8 Br cAMP) with or without the addition of interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-6, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), or transforming growth factor-beta (TGF-beta). Cells were then examined for morphologic changes and for expression of surface Gal and low-affinity nerve growth factor receptor (NGFRp75), employing indirect immunofluorescence. 8 Br cAMP induced Schwann cell upregulation of Gal, downregulation of NGFRp75, and the cells became enlarged and somewhat amorphous and irregular in appearance. Cells treated with IFN-gamma or TNF-alpha alone were more bipolar and more evenly distributed on coverslips than were control cells, whereas TGF-beta alone induced elongated cells often in a swirling pattern. None of the cytokines alone induced upregulation of Gal or downregulation of NGFRp75. TNF-alpha, IFN-gamma, and TGF-beta inhibited the 8 Br cAMP-induced morphologic changes, as well as the upregulation of Gal and downregulation of NGFRp75. The other cytokines had no effects on Gal or NGFRp75 expression. Thus, these three cytokines, which are present in inflammatory lesions in the peripheral nervous system, are capable of inhibiting Schwann cell differentiation.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2005

Apical membrane and junctional complex formation during simple epithelial cell differentiation of F9 cells.

Epithelium formation is a common event in animal morphogenesis. It has been reported that F9 cells differentiate into visceral endoderm-like epithelial cells when cell aggregates are cultured in the presence of retinoic acid. The present investigation set out to determine whether this in vitro model could be used under monolayer culture conditions, which is suitable for a detailed analysis of epithelial differentiation. We performed comparative gene expression analyses of F9 cells grown under aggregate and monolayer culture conditions prior to and following treatment with retinoic acid. Under these conditions, induction in the expression of differentiation marker genes was confirmed, even in monolayer cultures. Junctional complex and apical membrane formation, both of which are characteristic of epithelial cells, were also observed under monolayer culture conditions. Because of the merit of monolayer culture condition, we found that apical membrane and junctional complex formation are strictly regulated during epithelial differentiation. It was also revealed that F9 cells differentiated into epithelial cells predominantly on the fourth and fifth day following retinoic acid induction. These results showed that a monolayer culture of F9 cells represents a viable in vitro model that can be employed to elucidate mechanisms pertaining to epithelium formation.

Animals↗
PubMed1997

Cell renewal, cell differentiation and programmed cell death (apoptosis) in pilomatrixoma.

Pilomatrixoma is a benign tumour of the cutaneous adnexa. Histologically, pilomatrixoma comprises masses of immature basophilic cells, small numbers of polygonal squamoid cells, few transitional cells, and clusters of 'shadow cells'. The mechanism leading to the formation of shadow cells is still unknown. Skin biopsy specimens of pilomatrixoma (n = 15) were studied histologically, immunohistologically, and by applying the in situ end-labelling technique. The basal layer of the basophilic cells induced most of the proliferating cells with high expression of bcl-2 and cytokeratin 19. The overlying basophilic cells showed a negligible mitotic activity, a high significant accumulation of p53 protein, and a heterogeneous, but progressive loss of bcl-2 and cytokeratin 19. They developed either into squamoid cells or into transitional cells. The squamoid cells were characterized as differentiated cells resembling mature keratinocytes of stratified mucosa. The transitional cells could be shown to represent apoptotic cells proceeding to shadow cells. The data suggest that apoptosis is the main mechanism leading to the development of the dead shadow cells and is most probably responsible for the banal biological behaviour of pilomatrixoma. Apart from that, pilomatrixoma represents a suitable biological model to study apoptosis in humans.

Apoptosis↗
PubMed1991

Effects of protein kinase A and calcium/phospholipid-dependent kinase modulators in the process of HL-60 cell differentiation: their opposite effects between HL-60 cell and K-562 cell differentiation.

We have previously shown that HL-60 cells treated with 1 alpha, 25-(OH)2D3 in magnesium-deficient medium are committed to differentiate but do not express differentiation-related phenotypes. In the present study, we demonstrated that Mg2+ deprivation blocked the process of differentiation before the induction of lysozyme mRNA and that the process of HL-60 cell differentiation could be divided into two steps, i.e., a commitment step and a phenotypic expression step. We studied the effects of protein kinase A (PKA) and calcium/phospholipid-dependent protein kinase (PKC) modulators at each step. The results indicated that agonists of PKA enhanced both steps but that N-(2-[methylamino]ethyl-5-isoquinolinesulfonamide inhibited them. On the other hand, 1-oleyl-2-acetylglycerol and 12-O-tetradecanoylphorbol-13-acetate enhanced the commitment step but inhibited that of phenotypic expression. Staurosporine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine inhibited the commitment step and enhanced that of phenotypic expression. These results indicate that PKA acts as a positive regulatory signal and that PKC has a dual role in the process of HL-60 cell differentiation, i.e., as a positive regulatory signal in the commitment step and as a negative one in the phenotypic expression step. Recently, we have also shown that in K-562 cell differentiation into erythroid lineage, PKA may serve as a negative regulatory signal in both steps; however, PKC may act dually, namely as a negative regulatory signal in the commitment step and as a positive one in the phenotypic expression step.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗
PubMed2001

Reconstitution of cyclin D1-associated kinase activity drives terminally differentiated cells into the cell cycle.

Terminal cell differentiation entails definitive withdrawal from the cell cycle. Although most of the cells of an adult mammal are terminally differentiated, the molecular mechanisms preserving the postmitotic state are insufficiently understood. Terminally differentiated skeletal muscle cells, or myotubes, are a prototypic terminally differentiated system. We previously identified a mid-G(1) block preventing myotubes from progressing beyond this point in the cell cycle. In this work, we set out to define the molecular basis of such a block. It is shown here that overexpression of highly active cyclin E and cdk2 in myotubes induces phosphorylation of pRb but cannot reactivate DNA synthesis, underscoring the tightness of cell cycle control in postmitotic cells. In contrast, forced expression of cyclin D1 and wild-type or dominant-negative cdk4 in myotubes restores physiological levels of cdk4 kinase activity, allowing progression through the cell cycle. Such reactivation occurs in myotubes derived from primary, as well as established, C2C12 myoblasts and is accompanied by impairment of muscle-specific gene expression. Other terminally differentiated systems as diverse as adipocytes and nerve cells are similarly reactivated. Thus, the present results indicate that the suppression of cyclin D1-associated kinase activity is of crucial importance for the maintenance of the postmitotic state in widely divergent terminally differentiated cell types.

Animals↗
PubMed1992

Protein kinase C mRNA levels and activity in reconstituted normal human epidermis: relationships to cell differentiation.

Although keratinocytes are a major target of phorbol ester actions, the activity and the expression of the eight cloned protein kinase C (PKC) isoenzymes have not been studied in detail in human epidermis. Starting from normal human keratinocytes, we reconstituted in culture a multilayered epithelial tissue which presents many hystological, biochemical, and molecular features of the authentic epidermis and we used it as a model to investigate the PKC activity and mRNA levels. We found that i) PKC activity is higher in differentiated than in non-differentiated cells; ii) the mRNA levels of PKC delta and -eta/L, while are differently affected by spontaneous keratinocyte differentiation, are down-regulated during phorbol esters-induced cell differentiation. Our findings could represent a basis to investigate the involvement of PKC isoforms in the keratinocyte differentiation process.

Base Sequence↗
PubMed1982

White cell differential: coupling of cell types in patients undergoing chemotherapy.

The peripheral white blood cell differential counts in patients undergoing chemotherapy showed an unexpected partial correlation between the various cell classes during wide swings in the absolute cell number. These observations were made using the technique of automated flow cytochemistry on a 10,000 cell count Hemalog-D, which increases the statistical precision and permits differential counts in leukopenic patients. The data demonstrated that the white cell types do not behave as independent variables and suggest that the white blood cell differential count in the peripheral blood during chemotherapy may be in part altered by factors unrelated to cell production or destruction kinetics.

Antineoplastic Agents↗