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Results for “CELL DIFFERENTIATION”

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At least 415 records · Page 23Linked to original sources
PubMed1986

Thyrotropin-independent mutant clones from FRTL5 rat thyroid cells: hormonal control mechanisms in differentiated cells.

Mutant cells varying in the pathways of their responses to hormonal stimulation are useful in defining the subcellular steps in the mechanisms of hormone action. FRTL5, a strain of normal and differentiated cells originally derived from adult rat thyroids, which depends on TSH for growth in vitro, was used to produce five TSH-independent mutants, after chemical mutagenesis and selection in medium lacking TSH. Their characterization and comparison with wild type cells demonstrated full retention of differentiated thyroid function markers such as thyroglobulin production and active iodide transport, and a slower growth rate. Characterization of cAMP metabolism in mutants revealed levels of basal cAMP and adenylate cyclase and phosphodiesterase activities similar to those of wild type cells kept in a nonproliferative state in medium lacking TSH. Adenylate cyclase responsiveness to very low doses of TSH (10(-12) M) was fully retained in all mutant clones, but the TSH-dependent cAMP elevation, although comparable to that reported in wild type cells, was not followed by significant growth stimulation in mutants. These findings demonstrate that the persistence of functional TSH receptors in these cells and that of growth regulation in them is independent of cAMP elevation.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1987

Simultaneous enrichment of HL-60 cells in G1 and separation from differentiating cells by centrifugal elutriation for studies on differentiation induction.

Cultures of the promyelocytic leukemia cell line HL-60 usually contain considerable numbers of spontaneously differentiating cells and are asynchronous in terms of cell-cycle phases. Counterflow centrifugal elutriation studies have been conducted to obtain a homogeneous cell population with regard to cell-cycle phases and stage of differentiation. Despite their small volume and probably because of their high buoyant density, differentiated cells are elutriated predominantly at higher flow rates. Accordingly, G1 cells elutriated at low flow rates are substantially free from spontaneously differentiating cells. By optimizing the technique, a population with approx. 90% G1 cells and less than 1% spontaneously differentiating cells was obtained. The yield in the fractions chosen was 5.1% of all cells recovered from elutriation. In culture, a cell population of this purity maintains a synchronous cell cycle for more than 2 days. This allows an exact determination of the time after induction when the first signs of differentiation occur. The presence of 1 microM retinoic acid (RA) causes the first significant increase of NBT-positive cells between the 24th and 27th h of culture.

Cell Cycle↗
PubMed1999

Differential effect on U937 cell differentiation by targeting transcriptional factors implicated in tissue- or stage-specific induced integrin expression.

The inhibition of transcription factor functions was used to define their role in phorbol ester-induced cellular differentiation of a monocytic cell line, U937. We demonstrate a differential effect on cell adhesion and differentiation: antisense or competitive binding with double-stranded oligonucleotides antagonized the functions of AP-1, NF-kappaB, and PU.1 transcriptional factors. In the presence of phorbol 12-myristate 13-acetate (PMA), U937 cells attached to the plastic surface and cells were characterized by marked expression of beta2-integrin molecules on the cell surface. We show that the in vivo differentiation of U937 cells appears to occur normally in the absence of AP-1 activity. In contrast, the addition to the cell culture of phosphorothioate oligonucleotides that contained the NF-kappaB or PU.1 binding sites significantly inhibited U937 differentiation. The absence of NF-kappaB led to pleiotropic effects with a clear reduction in the expression of integrin and other lineage-specific myeloid antigens on the cell surface. In contrast, the absence of PU.1 had a more restricted effect on integrin expresion on the cell surface, probably as a result of blockage of CD18 gene expression.

CD18 Antigens↗
PubMed1994

Muscle cell differentiation of embryonic stem cells reflects myogenesis in vivo: developmentally regulated expression of myogenic determination genes and functional expression of ionic currents.

The mouse blastocyst-derived embryonic stem cell (ES cell) line BLC6 efficiently differentiates into myosin heavy chain-, desmin- and myogenin-positive skeletal muscle cells when cultivated in embryo-like aggregates (embryoid bodies). Here, we show that the muscle-specific determination genes myf5, myogenin, myoD, and myf6 are expressed in these embryoid bodies in a characteristic temporal pattern which precisely reflects the sequence observed during mouse development in vivo. Myf5 is the first gene to be expressed followed by myogenin, myoD, and myf6, in this order. In situ hybridization demonstrates transcripts for myogenin and myoD accumulating in mono- and multinucleated myogenic cells, while myf5 mRNA is already found in mononucleated myoblasts. The myocytes also express functional nicotinic cholinoceptors and exhibit T-type Ca2+ currents and later L-type Ca2+ currents, demonstrating physiological properties of skeletal muscle cells. During myocyte differentiation the density of L-type Ca2+ channels significantly increases while the density of T-type Ca2+ channels decreases. The effect of external signals on myogenic differentiation of BLC6 cells was demonstrated by cocultivation with visceral endodermal END-2 cells and the activin A-secreting WEHI-3 cells. END-2 cells essentially prevent skeletal muscle differentiation, whereas basic fibroblast growth factor, transforming growth factor-beta, and WEHI-3 cells have no or an attenuating effect, respectively. Our results suggest that ES cells recapitulate closely the early steps of muscle development in vivo and may serve as an excellent in vitro system to study this process.

Animals↗
PubMedDate not supplied

Ultrastructure of human embryonic stem cells and spontaneous and retinoic acid-induced differentiating cells.

Ultrastructural and immunohistochemical studies of 4 groups of cells-(human embryonic stem cells (hES), embryoid bodies (EB), and spontaneously and retinoic acid (RA)-induced differentiating cells)-were carried out to investigate their detailed phenotype. Immunohistochemically, the EB cells showed strong immunoreactivity for CD34, CD117, and nestin. Differentiating cells expressed pancytokertin, vimentin, CD31, CD56, GFAP, nestin, and NeuN as well as CD34, and c-Kit. However, synaptophysin and neurofilaments were not present in these same differentiating cells. Transmission electron microscopy showed that hES and EB cells were very similar to germ cells or cells of the inner cell mass. Spontaneously and RA-induced differentiating cells exhibited epithelial, mesenchymal, endodermal, and neuronal phenotypes. The perikarya of the neuronal cells had rich RERs (Nissl substance) and long cytoplasmic processes filled with numerous neural tubules. However, neither synaptic junctions nor synaptic vesicles were developed. In our study, RA treatment with brain-derived growth factor and TGFalpha in neuron differentiation medium induced not only neuronal differentiation but also pluripotential differentiation. Full neuronal differentiation did not occur after 2 weeks in culture, as no synaptic junctions and synaptic vesicles developed.

Antineoplastic Agents↗
PubMed1997

Lucké renal adenocarcinoma, an anuran neoplasm: studies at the interface of pathology, virology, and differentiation competence.

The northern leopard frog, Rana pipiens, is vulnerable to a herpesvirus-induced renal tumor. The Lucké renal adenocarcinoma is metastatic as a function of temperature. The cloning procedure of nuclear transplantation has been used to study the differentiation potential of the tumor genome. This paper summarizes current studies of the pathology, virology, and differentiation competence of the Lucké tumor.

Adenocarcinoma↗
PubMed1991

Monoclonal antibodies that block adhesion of B cell progenitors to bone marrow stroma in vitro prevent B cell differentiation in vivo.

B cell differentiation requires adhesion of B cell progenitors to bone marrow (BM) or fetal liver stroma. We show that B lymphoid cells can adhere to the BM stroma cell line CS 1.3, in vitro. Two monoclonal antibodies, SAB-1 and SAB-2, inhibited the adhesion of a B220+ progenitor B cell line but did not interfere with the binding of cytoplasmic mu chain-positive pre-B cells or mature B cells to the BM stromal cell line. Injection of both SAB-1 and SAB-2 antibodies into pregnant mice reduced by 90% the number of B220+n B lineage cells in the livers of their embryos. Livers from such embryos also were virtually devoid of cells able to give rise to B cell colonies in soft agar cultures (CFU-preB). Either antibody separately had no effect. Flow cytometry analysis show that SAB-1 is present on CS 1.3 stroma cells and on a pre-B cell line while SAB-2 is present on pro-B and pre-B cell lines, but not on CS 1.3 stromal cells. SAB-1 and SAB-2 react with different molecules and neither antibody seems to recognize CD44, and adhesion molecule that may also participate in B cell differentiation. Proteinase K and trypsin can digest both SAB-1 and SAB-2 antigens from viable cells suggesting that both are cell surface proteins. We propose that antibodies SAB-1 and SAB-2 probably recognize novel cell-cell adhesion molecules, and that these molecules are involved in the interactions between B cell progenitors and stroma cells.

Animals↗
PubMed2006

Involvement of suppressors of cytokine signaling in toll-like receptor-mediated block of dendritic cell differentiation.

Dendritic cells (DCs) are important sentinels within innate immunity, monitoring the presence of infectious microorganisms. They operate in 2 different maturation stages, with transition from immature to mature DCs being induced by activation of toll-like receptors (TLRs). However, TLRs are also expressed on precursor cells of DCs. Here we analyzed the effects of TLR stimulation during the process of granulocyte-macrophage-colony-stimulating factor (GM-CSF)-mediated in vitro generation of immature DCs from precursor cells. We show that TLR triggering deviated phenotypic and functional differentiation from CD14+ monocytes to CD1a+ DCs. Similar results were obtained when differentiation of murine myeloid DCs from bone marrow cells was analyzed. The inhibitory effects were independent of soluble factors. TLR stimulation in DC precursor cells induced proteins of the suppressor of cytokine signaling family (SOCS), which correlated with loss of sensitivity to GM-CSF. Overexpression of SOCS-1 abolished GM-CSF signal transduction. Moreover, forced SOCS-1 expression in DC precursors mimicked the inhibitory effects on DC generation observed for TLR stimulation. The results indicate that TLR stimulation during the period of DC generation interferes with and deviates DC differentiation and that these effects are mediated particularly by SOCS-1.

Animals↗
PubMed2005

Inhibition of T cell differentiation into effectors by NKT cells requires cell contacts.

NKT cells are potent regulatory T cells that prevent the development of several autoimmune diseases. Analysis of NKT cell regulatory function in the NOD mouse has revealed that NKT cells inhibit the development of type 1 diabetes by impairing the differentiation of anti-islet T cells into Th1 effector cells. In the present study, we have performed in vitro and in vivo experiments to determine the respective role of cytokines and cell contacts in the blockade of T cell differentiation by NKT cells. These experiments reveal that cytokines such as IL-4, IL-10, IL-13, and TGF-beta, that have been involved in other functions of NKT cells, play only a minor role if any in the blockade of T cell differentiation by NKT cells. Diabetes is still prevented by NKT cells in the absence of functional IL-4, IL-10, IL-13, and TGF-beta. In contrast, we show for the first time that cell contacts are crucial for the immunoregulatory function of NKT cells.

Animals↗
PubMed2005

Adeno-associated virus-mediated bone morphogenetic protein-7 gene transfer induces C2C12 cell differentiation into osteoblast lineage cells.

AIM: To investigate the effects of bone morphogenetic protein-7 (BMP7)-expressing recombinant adeno-associated virus (AAV) vector on the differentiation of C2C12 cells. METHODS: AAV-BMP7 was packaged by infecting the stable cell clone BHK-21 (integrated with recombinant AAV vector plasmid pSNAV-BMP7) with recombinant herpes simplex virus type 1, which expresses AAV-2 Rep and Cap and possesses AAV packaging functions. Following infection with AAV-BMP7 at multiplicities of infection of 1 x 10(5) vector genomes per cell and subsequent culture, C2C12 cells were assessed qualitatively for BMP7 production, alkaline phosphatase activity, osteocalcin production and Cbfal and MyoD expression. RESULTS: C2C12 cells transduced with AAV-BMP7 could produce BMP7 protein until d 28. Alkaline phosphatase in the cultured C2C12 cell lysate was elevated. Secreted osteocalcin in the culture medium was detectable at d 12 and Cbfal mRNA expression level was upregulated, coinciding with downregulation of MyoD in a temporal manner. CONCLUSION: The present in vitro study demonstrated that AAV-BMP7 could infect and efficiently convert C2C12 cells from myoblasts into osteoblast lineage cells.

Alkaline Phosphatase↗
PubMed2002

Interferon-alpha induces dendritic cell differentiation of CML mononuclear cells in vitro and in vivo.

The ability of interferon-alpha (IFN-alpha) to induce dendritic cell (DC) differentiation in chronic myeloid leukemia (CML) was evaluated. Peripheral blood mononuclear cells from CML patients cultured with IFN-alpha and granulocyte-macrophage colony-stimulating factor (GM-CSF) developed a dendritic morphology. Fluorescence in situ hybridization demonstrated that the DCs harbored the bcr/abl translocation. The DCs prepared with IFN-alpha/GM-CSF expressed significantly higher levels of class I and II HLA than those grown in interleukin-4 (IL-4) and GM-CSF. The DCs prepared from newly diagnosed CML patients using IFN-alpha/GM-CSF expressed immunoregulatory proteins at levels comparable to normal DCs. In contrast, DCs cultured from CML patients who did not achieve a cytogenetic response to IFN-alpha expressed significantly lower levels of class I HLA, CD40, CD54, CD80 and CD86 than normal DCs. The expression of CD86 by CML DCs was enhanced when they were cultured with IFN-alpha/IL-4/GM-CSF, or when IFN-alpha/GM-CSF-treated cells were induced to mature by CD40 ligand. The DCs from IFN-alpha failures were less stimulatory than normal DCs in the allogeneic mixed leukocyte reaction. CML patients who had a cytogenetic response to IFN-alpha initially had low numbers of bone marrow DCs that increased significantly with treatment, while nonresponders had more prevalent DCs at baseline that showed no consistent change with treatment. Therefore, IFN-alpha can induce DC differentiation from CML progenitor cells both in vitro and in vivo. The therapeutic activity of IFN-alpha in CML may be due to its ability to stimulate the generation of DCs that can present CML-specific antigens. Resistance to IFN-alpha may result when DC differentiation becomes impaired.

Antigen Presentation↗
PubMed1980

The critical role of the nucleolus in cell differentiation and stem cell development - the concept as it applies to erythropoiesis.

There is evidence to suggest that nucleated red blood cells (normoblasts) are derived from a fixed reticulum cell lining that marrow sinusoids. The reticulum cell is transformed into a nucleolated stem cell which gives rise to a cluster of normoblasts by a special process of clonal division. The problem, which is paramount to myeloid development, is what happens to the large numbers of nuclei which are extruded from the normoblasts during the freeing of the haemoglobinised plastid. They seem to disappear without a trace, and in order to explain this phenomenon the hypothesis is made that the extruded nuclei are transformed into cells of the neutrophil series, and evidence is presented to support this viewpoint.

Animals↗
PubMed2004

Cell sorting by differential cell motility: a model for pattern formation in Dictyostelium.

In the slug stage of the cellular slime mold Dictyostelium discoideum, prespore cells and four types of prestalk cells show a well-defined spatial distribution in a migrating slug. We have developed a continuous mathematical model for the distribution pattern of these cell types based on the balance of force in individual cells. In the model, cell types are assumed to have different properties in cell motility, i.e. different motive force, the rate of resistance against cell movement, and diffusion coefficient. Analysis of the stationary solution of the model shows that combination of these parameters and slug speed determines the three-dimensional shape of a slug and cell distribution pattern within it. Based on experimental data of slug motive force and velocity measurements, appropriate sets of parameters were chosen so that the cell-type distribution at stationary state matches the distribution in real slugs. With these parameters, we performed numerical calculation of the model in two-dimensional space using a moving particle method. The results reproduced many of the basic features of slug morphogenesis, i.e. cell sorting, translocation of the prestalk region, elongation of the slug, and its steady migration.

Animals↗
PubMed1984

Renin storage and cell differentiation in juxtaglomerular cell tumors: an immunohistochemical and ultrastructural study of three cases.

Three renin-secreting juxtaglomerular cell tumors were studied by ultrastructural and immunocytochemical methods. Both active and inactive renins were identified in tumor extracts. By immunofluorescence and the peroxidase-antiperoxidase (PAP) method with antirenin antiserum, immunolabeling was intracytoplasmic and irregularly distributed throughout the tumor tissue. Electron microscopic examination revealed various types of secretory granules, including atypical giant crystalloid protogranules in one case, and the postembedding PAP procedure showed labeling of all types of granules. Acid phosphatase staining was observed within secretory granules and autophagic vacuoles. The process of renin storage and release is discussed. The presence in one case of a neural component and a distal tubular structure supports the view of a hamartomatous lesion.

Adult↗
PubMed1999

[Cell count and differential cell count in goat milk--variability and influencing factors].

In a total of 413 dairy goats of different breeds from five herds (milk performance 550-1000 kg) somatic cell counts and cell types were investigated in fore milk samples from udder halves, in composed udder and bulk milk samples. Cytoplasmatic particles in the milk were not counted. Three herds were investigated monthly during two years. At every sampling a clinical examination of the mammary gland (fore milk, teats, gland tissue, lymphatic nodes of the udders) and a bacteriological examination of the milk samples were carried out. In all herds the clinical health status of the udders was good. Independent of the sample type the mean SCC was about 1000 x 10(3)/ml with a wide range between several millions and < 100,000/ml. A seasonal influence on the monthly minima and maxima of the bulk milk SCC was evident, the lower SCC being recorded mainly during April to October. Increasing lactation numbers and months are connected with increasing SCC. Goats with high milk SCC at the begin of the lactation tended to maintain their high SCC levels as the lactation progressed. Limit values for SCC in goat milk should take into account the influence of the kidding season of the herds upon the dynamics of the bulk milk SCC. Polymorphonuclear leukocytes were the main cell type in goat milk (around 40%), their number tended to increase as total SCC increased, in particular in samples with cell counts above one million. Likewise, the differences between SCC in the milk of corresponding udder halves increased significantly as one of the halves showed more than one million somatic cells. Defining limit values for SCC in goat milk this should be taken into account.

Animals↗
PubMed2005

Pax3 functions at a nodal point in melanocyte stem cell differentiation.

Most stem cells are not totipotent. Instead, they are partially committed but remain undifferentiated. Upon appropriate stimulation they are capable of regenerating mature cell types. Little is known about the genetic programmes that maintain the undifferentiated phenotype of lineage-restricted stem cells. Here we describe the molecular details of a nodal point in adult melanocyte stem cell differentiation in which Pax3 simultaneously functions to initiate a melanogenic cascade while acting downstream to prevent terminal differentiation. Pax3 activates expression of Mitf, a transcription factor critical for melanogenesis, while at the same time it competes with Mitf for occupancy of an enhancer required for expression of dopachrome tautomerase, an enzyme that functions in melanin synthesis. Pax3-expressing melanoblasts are thus committed but undifferentiated until Pax3-mediated repression is relieved by activated beta-catenin. Thus, a stem cell transcription factor can both determine cell fate and simultaneously maintain an undifferentiated state, leaving a cell poised to differentiate in response to external stimuli.

Aging↗