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At least 37 records · Page 2Linked to original sources
PubMed1979

Cell differentiation in isolated inner cell masses of mouse blastocysts in vitro: onset of specific gene expression.

Inner cell masses (ICMs) were isolated by immunosurgery from giant blastocysts formed by the aggregation of three morulae. A layer of endoderm cells formed on the outer surface of these primary ICMs in vitro. When this layer was removed by immunosurgery, a secondary endoderm layer formed. Alphafetoprotein (AFP) was used as a biochemical marker to characterize visceral endoderm formation in these cultured ICMs. The immunoperoxidase reaction on sections of ICMs cultured for intervals up to 120 h in vitro showed that some primary endoderm cells contained AFP, but these were always in the minority. The secondary endoderm layer, on the other hand, was composed of predominantly AFP-positive cells. It is concluded that the primary endoderm contains mainly parietal endoderm cells, while the secondary layer contains visceral endoderm cells. A model is proposed for the consecutive differentiation of parietal and visceral endoderm cell types from the ICM of mouse blastocysts.

Animals↗
PubMed1978

Regulation of interstitial cell differentiation in Hydra attenuata. III. Effects of I-cell and nerve cell densities.

The interstitial cell (i-cell) of hydra, a multipotent stem cell, produces two classes of differentiated cell types, nerve cells and nematocytes, throughout asexual growth. Using a new assay, the regulation of i-cell commitment to either nerve cell or nematocyte differentiation was investigated. This assay was used to determine the fractions of i-cells differentiating into nerve cells and nematocyte precursors in a variety of in vivo cellular milieus produced by hydroxyurea treatment, differential feeding, and reaggregation of dissociated cells. Nematocyte commitment was found to be positively correlated with the size of the i-cell population and independent of the axial position of the i-cells along the body column. This indicates that i-cell commitment to nematocyte differentiation may be regulated by feedback from the i-cell population. Nerve cell commitment was found to be correlated with regions of high nerve cell density. This suggests that nerve cell commitment is regulated by feedback from the nerve cell population or is dependent on axial position. Implications of such mechanisms for the regulation of i-cell population size and distribution are discussed.

Animals↗
PubMed1979

Suppression of adult B cell differentiation in pokeweed mitogen-stimulated cultures by Fc(IgG) receptor-negative T cells from cord blood.

Unfractionated T lymphocytes from cord blood suppressed adult B cell differentiation into immunoglobulin-producing cells in pokeweed mitogen-stimulated co-culture system. Cord blood T cells were fractionated into T cells bearing Fc receptors for IgG (Tgamma cells) and T cells lacking Fc receptors for IgG(Tnon-gamma cells) by rosette formation with ox erythrocytes coated by the IgG fraction of rabbit antisera followed by Ficoll-Hypaque gradient sedimentation. T gamma cells from cord blood, even though isolated after the interaction with immune complexes, showed no suppressor activity on adult B cell differentiation, whereas Tnon-gamma cells exerted strong suppression to a similar extent to that by unfractionated cord T cells. The suppressor activity on B cell differentiation by Tnon-gamma cell as well as by unfractioned T cells from cord blood was completely abrogated by irradiation with 2000 rads. These results indicated that, contrary to suppressor function found in adult T cells, the suppressor activity in cord T cells might be exerted by a T cell subset lacking Fc receptors for IgG(Tnon-gamma cells).

Adult↗
PubMed1979

Chromatin conformation during cell differentiation of human myeloid leukemia cells.

A novel human promyelocytic leukemia cell line (HL-60) has been shown to form terminally differentiated granulocytes in the presence of dimethyl-sulfoxide (DMSO), some other chemicals, or colony stimulating factor. Compared to chromatin from HL-60 cells, chromatin from DMSO treated HL-60 cells showed an enrichment in low temperature melting material. The decrease in thermostability of chromatin from HL-60 cells after DMSO treatment is similar to the shift in thermostability of chromatin from human lymphocytes after stimulation with phytohemagglutinin (PHA). These results suggest that changes in the thermostability of chromatin may not be specific for cell differentiation or PHA stimulation.

Adult↗
PubMed2026

TGF-β and IL-2 differentially shape T follicular regulatory cell differentiation and stability in vitro.

T follicular helper (Tfh) cells and T follicular regulatory (Tfr) cells play critical roles in regulating the activity of the germinal center (GC), which is essential for the generation of high-affinity antibodies. In the GC, Tfh cells help B cells to proliferate and to differentiate into memory B cells and long-lived plasma cells. In contrast, Tfr cells, a specialized subset of regulatory T cells (Tregs), modulate the humoral immune response by suppressing excessive or autoreactive B-cell activity. Here, we established an in vitro differentiation protocol for mouse CD4⁺ T cells that yielded CXCR5⁺FoxP3⁺ Tfr cells that exhibited a Bcl6hiPD-1hiCD25loGITRint phenotype and were distinct from Treg and Tfh cells. Functionally, in vitro-generated Tfr cells potently suppressed Tfh cell-driven B-cell class switching to IgG1 and downregulated the expression of B-cell costimulatory ligands. While in vitro-generated Bcl6-deficient Tfh cells were impaired in providing help to B cells for efficient class switching to IgG1, in vitro-generated Bcl6-deficient Tfr cells failed to inhibit Tfh cell-driven B-cell class switching to IgG1. Mechanistically, we showed that Tfr cells emerged from FoxP3+ precursors in low-IL-2 environments through a TGF-β- and c-Maf-dependent pathway, allowing for reprogramming and reinforcement of the follicular regulatory cell program in CD4+ T cells in vitro.

Animals↗
PubMed1978

Regulation of interstitial cell differentiation in Hydra attenuata. IV. Nerve cell commitment in head regeneration is position-dependent.

In hydra, nerve cells are a differentiation product of the interstitial cell, a multipotent stem cell. Nerve cell commitment was examined during head regeneration in Hydra attenuata. Within 3 h of head removal there is a 10- to 20-fold increase in nerve cell commitment in the tissue which subsequently forms the new head. Nerve cell commitment is unaltered in the remainder of the gastric region. This local increase in nerve cell commitment is responsible for about one half the new nerve cells formed during head regeneration, while one half differentiate from interstitial cells that migrate into the regenerating tip.

Animals↗
PubMed1978

Colchicine induces multiple axis formation and stalk cell differentiation in Dictyostelium discoideum.

Colchicine is shown to have several effects on the development of the pseudoplasmodia of the cellular slime mould Dictyostelium discoideum. At concentrations of 0.01 M and above culmination was prevented, while differentiation of cells into stalk cells occurred at the rear of cell masses. Essentially all cells transformed into stalk cells when slugs were left on colchicine agar for a long time. At concentrations of 0.01 M normal slug architecture was maintained while above 0.025 M pseudoplasmodia reorganized into multiple mounds. Each of these mounds developed an apparently normal discrete tip which was devoid of prespore cells as shown by immunofluorescent staining. The same effects were observed in growing cultures and in regulating slugs treated with colchicine. The data are consistent with the ideas that microtubules are involved in the maintenance of slug architecture and in the differentiation of stalk cells. The modes by which these intracellular structures may operate in these functions are discussed.

Animals↗
PubMedDate not supplied

[Metabolism of nuclear proteins during hormone-dependent cell differentiation in the mammae of goats].

The metabolism of nuclear proteins was studied at differentiation of mammary cells in the tissue culture with lactogenic hormones. The synthesis of nuclear acidic proteins under the influence of insulin is shown to be an initial step in cell differentiation of the gland; later the DNA synthesis is stimulated, and the synthesis and phosphorylation of histones are intestified. The inducing action of prolactin on the synthesis of RNA and casein is displayed only after the action of insulin and hydrocortisone on the tissue.

Animals↗
PubMed2026

PDLIM4 promotes dephosphorylation of STAT transcription factors by recruiting PTP-BL and inhibits Th1, Th2, and Th17 cell differentiation.

STAT (signal transducers and activators of transcription) transcription factors are activated by tyrosine phosphorylation after cytokine stimulation and are critical for the differentiation of T-helper (Th) cells into particular Th lineage subsets. How STAT-mediated Th cell differentiation is negatively regulated, however, is not fully understood. Here, we report that PDLIM4 binds to STAT3, 4, and 6 and suppresses gene activation mediated by these STATs. PDLIM4 acts as an adaptor that recruits PTP-BL, a protein tyrosine phosphatase, through its LIM (abnormal cell lineage 11-islet 1-mechanosensory abnormal 3) domain, facilitating dephosphorylation of STAT proteins. PDLIM4-deficiency in CD4+ T cells resulted in augmented tyrosine phosphorylation of these STAT proteins and consequently enhanced Th1, Th2, and Th17 cell differentiation, suggesting that PDLIM4 regulates the differentiation of multiple lineages of Th cells by suppressing STAT signaling. We further found that a non-synonymous single-nucleotide polymorphism in PDLIM4, which causes the substitution of a glycine residue with a cysteine in the LIM domain, is associated with susceptibility to rheumatoid arthritis and Graves' disease, both of which are known to be Th17 cell-driven autoimmune diseases. Notably, PDLIM4 containing this amino acid substitution in the LIM domain showed reduced binding to PTP-BL and was therefore partially impaired in its ability to dephosphorylate STAT3 and suppress STAT3 signaling. Our findings define an essential role of PDLIM4 in negatively regulating STAT-mediated Th-cell differentiation and preventing the onset of human autoimmune diseases.

Animals↗
PubMed1977

Appearance of free histones within nuclei of differentiating cells in the developing rat embryo.

Having applied the picric acid-bromphenol blue (BPB) and the phosphomolybdic acid-benzidine (PMA-B) methods--the first method detecting the total histone content, the second one only free histones--we have found that cell nuclei of the rat embryos permanently contain histones, nevertheless, in such a pattern that the free histone appears only at a well-defined stage of embryogenesis. Strong PMA-B reaction is observable in the nuclei of some mesenchymal cells and in the reorganizing somites' cell nuclei of the 13-day-old embryo as well as in the hemopoietic elements of the 15- and 17-day old embryos' liver. Within nuclei of the red blood cells of the 13-day-old embryo an extremely intense reaction is seen which then disappears till the 15th day, while the BPB reaction shows a gradual intensification up to the neonatal age. The experiments support the former model of one of the authors for a histone-nonhistone control of ontogenesis.

Age Factors↗
PubMed1977

Regulation of phospholipid metabolism in differentiating cells from rat brain cerebral hemispheres in culture. Serine incorporation into serine phosphoglycerides: base exchange and decarboxylation patterns.

The patterns of serine metabolism into phospholipids of cultured brain cells was examined. Labeled serine was incorporated predominantly into serine- ad ethanolamine-containing phospholipids and sphingolipids. The highest rates of labeling were observed in the (1)acyl-(2)acyl- and (1)alkyl-(2)acyl-serine phosphoglyceride fractions. Serine incorporation into both compounds appears to proceed via a base exchange mechanism. A decrease in the rate of serine phosphoglycerides labeling and a depletion of the ATP levels were observed when oligomycin or the calcium ionophore A23187 was added to the incubation medium. The inhibition of serine incorporation by A23187 could be partially reversed following addition of 10 mM CaCl2. Based on these findings it is suggested that in addition to demonstrating the energy-independent calcium-stimulated pathway, there may also be an energy related pathway. Formation of ethanolamine phosphoglycerides, as a result of serine phosphoglycerides decarboxylation, has been analyzed by using a simplified compartmental model. Of the 0.67 nmol/mg of protein turned over per h in the diacylserine phosphoglyceride compartment, 0.14 nmol/mg of protein are converted into the ethanolamine phosphoglycerides. In a similar manner, of the 0.09 nmol/mg of protein turned over per h in the (1)alkyl-(2)acyl-serine phosphoglyceride compartment, 0.014 nmol/mg of protein is converted into the (1)alkyl-(2)acyl-ethanolamine phosphoglyceride. These figures provide a first indication that a considerable portion of the ethanolamine phosphoglycerides in cultured brain cells is formed via a direct decarboxylation of the serine phosphoglycerides. In estimating the rates of (1)alkenyl-(2)acyl-ethanolamine phosphoglyceride formation from (1)alkyl-(2)acyl-ethanolamine phosphoglyceride the precursor-product specific activity crossover point could not be established. Mathematical analysis, however, enabled us to estimate the flux from the former into the latter as 0.04 nmol/mg of protein per h. A scheme for the possible metabolic interconversions of the ether bond containing serine and ethanolamine phosphoglycerides is proposed.

Adenosine Triphosphate↗
PubMed1976

Biochemical aspects of cardiac muscle differentiation. Possible control of deoxyribonucleic acid synthesis and cell differentiation by adrenergic innervation and cyclic adenosine 3':5'-monophosphate.

A single injection of either isoproternol or N6, O2'-dibutyryl adenosine 3':5'-monophosphate (dibutyryl cyclic AMP) results in an inhibition in the rate of [3H]thymidine incorporation into DNA of differentiating cardiac muscle of the neonatal rat. This inhibition is not due to substantially altered cellular uptake or catabolism of [3H]thymidine. Inhibition of [3H]thymidine incorporation by isoproterenol or dibutyryl cyclic AMP is potentiated by theophylline. Maximal inhibition (95%) is observed 24 h after administration of isoproterenol, and the rate of incorporation returns to a value 80% of control by 72 h. Norepinephrine also inhibits [3H]thymidine incorporation whereas cyclic GMP, N2, 02-Dibutyryl guanosine 3':5'-monophosphate (dibutyryl cyclic GMP), and phenylephrine have little effect. Equilibrium sedimentation analysis of cardiac muscle DNA in neutral and alkaline cesium chloride gradients using bromodeoxyuridine as a density label indicate that isoproterenol and dibutyryl cyclic AMP inhibit [3H]thymidine incorporation into DNA that is replicating semiconservatively. Administration of isoproterenol or dibutyryl cyclic AMP to neonatal rats inhibits by approximately 60% the incorporation of [3H]thymidine into DNA of tissue slices of cardiac muscle prepared 16 h later. [3H]Thymidine incorporation into DNA of tissue slices is into chains that were growing in vivo. This incorporation is linear for at least 4 h of incubation and is inhibited by isoproterenol and dibutyryl cyclic AMP. Inhibition is not due to altered cellular uptake of [3H]thymidine nor is it due to a cytotoxic action. Several other compounds which elevate intracellular levels of cyclic AMP (epinephrine, norepinephrine, glucagon, and prostaglandin E1) also inhibit [3H]thymidine incorporation into DNA or cardiac muscle tissue slices. Cyclic GMP, dibutyryl cyclic GMP, sodium butyrate, and phenylephrine have little effect. Isoproterenol administered together with theophylline to neonatal rats signficantly stimulates the in corporation of [3H]phenylalanine into total cardiac muscle protein and into myosin. This enhanced incorporation may be due in part to an increase in the cellular uptake of [3H]phenylalanine. DNA synthesis decreases progressively in differentiating cardiac muscle of the rat during postnatal development and essentially ceases by the middle of the third week (Claycomb, W. C. (1975) J. Biol. Chem. 250, 3229-3235). In reviewing the literature it was found that this decline in synthetic activity correlates temporally with a progressive increase in tissue concentrations of norepinephrine and cyclic AMP and with the anatomical and physiological development of the adrenergic nerves in this tissue. Because of these facts and data presented in this report it is proposed that cell proliferation and cell differentiation in cardiac muscle may be controlled by adrenergic innervation with norepinephrine and cyclic AMP serving as chemical mediators.

Aging↗
PubMed1978

Three stages of erythropoietic progenitor cell differentiation distinguished by a number of physical and biologic properties.

Previous studies have shown that erythroid precursors at sequential stages of differentiation along the red cell pathway can be distinguished by differences in the size and maturation kinetics of the colonies to which they give rise in vitro. Using criteria based on these two parameters, it is thus possible to identify three distinct erythroid progenitor cell populations in the mouse, known as day 8 BFU-E, day 3 BFU-E, and CFU-E. These cell types have now been shown to differ in a number of other respects, including progenitor cell size, sensitivity to cycle-active agents, response to plethora, and effects of the W/Wv genotype. In addition, a comparison of the differences found between day 8 BFU-E and day 3 BFU-E on one hand and those distinguishing day 3 BFU-E and CFU-E on the other provides support for the view that early erythropoietic cell differentiation involves a series of changes that take place long before competence to synthesize hemoglobin becomes manifest.

Animals↗
PubMedDate not supplied

Cytomorphologic and cytochemical aspects of malignant histiocytosis with spindle-cell differentiation. A case report.

Spindle-cell differentiation and tumor formation have been observed rarely in cases of malignant histiocytosis. We describe below one case of malignant histiocytosis with spindle-cell differentiation. Touch preparation of autopsy material revealed cytologic features that correlated with the histologic appearance of atypical components of this entity, such as spindle and nonspindle histiocytes and abundant erythrophagocytosis. Cytochemical properties indicated the histiocytic nature of the cells that composed this tumor. A morphologic account of the different types of cells is presented.

Child↗