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 199 records · Page 11Linked to original sources
PubMed1984

Cord blood B cell differentiation. Synergistic effect of pokeweed mitogen and Staphylococcus aureus on in vitro differentiation of B cells from human neonates.

B lymphocyte differentiation into immunoglobulin secreting cells is a process depending on the presence of functionally mature B lymphocytes, monocytes and regulatory T lymphocytes. Cord blood B lymphocytes present in isolated cord blood mononuclear cell (MNC) preparations are normally unable to differentiate into immunoglobulin secreting plaque forming cells (PFC) when cultured in the presence of pokeweed mitogen (PWM) alone or killed Staphylococcus aureus Cowan 1 (SAC1) alone. However, each one of these activators induces PFC formation by B lymphocytes in adult MNC cultures. In the present study we show that these two activators can act synergistically to induce a significant in vitro PFC response in cord blood MNC's. The synergism of PWM and SAC1 exhibits a requirement for a specific sequence of addition in order to induce a positive response in neonatal cells. If both activators are not added simultaneously at the initiation of culture, only the initial addition of SAC1 followed by PWM will result in increased PFC production. The action of PWM and SAC1 on cord blood MNC can each be replaced by conditioned media. Supernatants from monocyte cultures containing soluble factors such as interleukin-1 (IL-1) can substitute for the activity of SAC1 while supernatants containing soluble T-cell factors (interleukin-2[IL-2], T cell replacing factor (TRF), B cell differentiation factor (BCDF), etc) can replace PWM in the cord blood MNC cultures. The results suggest that the synergistic effect of these two activators overcomes a partial immaturity or an excessive suppressor activity of human cord blood MNC.

Adult↗
PubMed2001

The transcriptional repressor CDP (Cutl1) is essential for epithelial cell differentiation of the lung and the hair follicle.

The mammalian Cutl1 gene codes for the CCAAT displacement protein (CDP), which has been implicated as a transcriptional repressor in diverse processes such as terminal differentiation, cell cycle progression, and the control of nuclear matrix attachment regions. To investigate the in vivo function of Cutl1, we have replaced the C-terminal Cut repeat 3 and homeodomain exons with an in-frame lacZ gene by targeted mutagenesis in the mouse. The CDP-lacZ fusion protein is retained in the cytoplasm and fails to repress gene transcription, indicating that the Cutl1(lacZ) allele corresponds to a null mutation. Cutl1 mutant mice on inbred genetic backgrounds are born at Mendelian frequency, but die shortly after birth because of retarded differentiation of the lung epithelia, which indicates an essential role of CDP in lung maturation. A less pronounced delay in lung development allows Cutl1 mutant mice on an outbred background to survive beyond birth. These mice are growth-retarded and develop an abnormal pelage because of disrupted hair follicle morphogenesis. The inner root sheath (IRS) is reduced, and the transcription of Sonic hedgehog and IRS-specific genes is deregulated in Cutl1 mutant hair follicles, consistent with the specific expression of Cutl1 in the progenitors and cell lineages of the IRS. These data implicate CDP in cell-lineage specification during hair follicle morphogenesis, which resembles the role of the related Cut protein in specifying cell fates during Drosophila development.

Alleles↗
PubMed1998

Mesonephric stromal cells differentiate into Leydig cells in the mouse fetal testis.

Circumstantial evidence has suggested that Sry expression probably occurs in pre-Sertoli cells, implying that they produce signals required for testis differentiation. From experiments involving gonad/mesonephros grafts it has been shown that, at 11.5 days postcoitum stromal cells from the mesonephros invade the male gonad. Although in the grafted testes, Leydig cells appeared among the stromal cells, in these studies their origin remained elusive. In the current study, we reconstructed urogenital ridges in organ culture by grafting morphologically undifferentiated male genital ridges from CD-1 embryos, to mesonephroi from ROSA26 transgenic embryos whose cells express the bacterial beta-galactosidase. With an improved technique for the detection of beta-gal enzyme activity in electronmicrographs, we studied cell migration and differentiation of mesonephric cells into the testis in reconstructed urogenital ridges with XY or XX mesonephroi. It was found that, in addition to differentiation of myoid and connective cells, some migratory mesonephric cells acquired ultrastructural features of steroidogenic Leydig cells. Several beta-gal positive cells differentiated as Leydig cells in gonads grafted with either male or female mesonephros. The results suggest that mesonephric cells responded to putative signal(s) produced in the male gonad and participate in morphogenesis and cell differentiation of the fetal testis.

Animals↗
PubMed1994

Lower mutation frequencies are induced by ENU in undifferentiated embryonic cells than in differentiated cells of the mouse in vitro.

The pluripotent embryonic carcinoma cells of line P19 established from undifferentiated cells of the early mouse embryo and their differentiated progeny, the epithelioid ectoderm-like EPI-7 cells, were investigated for the induction of mutations at the HPRT locus by the alkylating agent N-ethyl-N-nitrosourea (ENU). We showed that the cytotoxic effects of ENU after a 5-h treatment were lower in undifferentiated P19 cells than in differentiated EPI-7 cells. The IC50 values of ENU in the two cell lines amounted to 0.6 mg/ml and 0.09 mg/ml for P19 and EPI-7 cells, respectively. The induction of 6-thioguanine-resistant mutants by ENU (1.0 mg/ml) determined after an expression time of 8 days for both cell lines resulted in similar mutation frequencies. Using expression times of 8 days for P19 and 11.75 days for EPI-7 cells, taking into account the longer generation time of differentiated EPI-7 cells (13.7 +/- 3.6 h) in comparison to undifferentiated P19 cells (9.3 +/- 0.9 h), ENU induced significantly higher mutant frequencies in EPI-7 cells (4865 mutants/10(6) cells) than in P19 cells (282 mutants/10(6) cells). Our results and data from the literature on UV irradiation-induced repair support the idea that the induction of lower mutation frequencies in embryonic cells may correlate with different proliferation capacities, cell cycle parameters and/or different mechanisms of DNA repair in embryonic stem cells and differentiated cells, respectively.

Animals↗
PubMed1991

Monoclonal antibody against the human peripheral lymph node homing receptor homologue (Leu 8) inhibits B cell differentiation but not B cell proliferation.

Previous studies have shown that a subpopulation of circulating human B cells expresses the Leu 8 peripheral lymph node homing receptor homologue and that these B cells are capable of producing Ig in response to staphylococcus A Cowan I (SAC). In the present study the effect of a signal delivered via the Leu 8 molecule (using anti-Leu 8 mAb) on B cells was examined. Initially, it was shown that immobilized anti-Leu 8 suppressed IgM and IgG secretion of B cells activated by SAC + IL-2 but not that by PWM-prestimulated B cells or B cells stimulated with PWM in the presence of CD4+, Leu 8- T cells (a source of helper cells). It was also shown that anti-Leu 8 did not suppress SAC + IL-2-stimulated B cell proliferation or expression of IL-2R alpha-chain or c-myc mRNA in B cells. The addition of T cells, monocytes, purified IL-2, rIL-1, rIL-6, or human B cell growth factor did not overcome the inhibitory effect of anti-Leu 8 on SAC-stimulated B cell Ig production, and the inhibitory effect of anti-Leu 8 was not blocked by anti-TGF-beta. Finally, inhibition of B cell differentiation occurred even when anti-Leu 8 was added up to 72 hrs after initiation of cell culture. Thus, anti-Leu 8 is unique among inhibitors of B cell function in that it can down-regulate immunoglobulin synthesis without affecting B cell proliferation. These findings suggest that a natural ligand for Leu 8 could affect not only homing of B cells, but also B cell differentiation.

Antibodies, Monoclonal↗
PubMed2004

Beta1 integrin mediation of myogenic differentiation: implications for satellite cell differentiation.

Myoblast-extracellular matrix interactions mediated by integrin receptors have been shown to play a pivotal role in skeletal muscle development. In the current study, the avian genetic muscle weakness, low score normal (LSN), which exhibits modified myotube and sarcomere structure and a reduction in beta1 integrin expression during satellite cell differentiation, was used as a model system to further investigate the role of beta1 integrins in myogenic differentiation. During normal satellite cell differentiation, the beta1 integrin was localized at areas of pseudopodial activity and points of cell contact. In contrast, in LSN satellite cell cultures the beta1 integrin was predominantly observed in clusters not associated with points of cell to cell contact. The LSN satellite cells underwent apoptosis at the same time normal satellite cells were fusing to form multinucleated myotubes. During muscle development, the beta1 integrin is regulated by alternative splicing from a beta1A to beta1D form. During both embryonic and posthatch pectoralis major muscle development, regulation of the beta1A and beta1D variants was altered in the LSN. Normal and LSN myogenic satellite cell cultures did not express the beta1D integrin, but the LSN satellite cells expressed higher concentrations of the beta1A integrin than did normal satellite cells. Taken together, these data further demonstrate the importance of the beta1 integrin subunit in the regulation of cell-extracellular matrix signal transduction pathways during muscle growth and differentiation.

Amino Acid Sequence↗
PubMed1982

Human B cell differentiation. III. Enhancing effect of monoclonal anti-immunoglobulin D antibody on pokeweed mitogen-induced plasma cell differentiation.

The effects of monoclonal anti-delta antibodies on pokeweed mitogen (PWM) responses of blood mononuclear cells (MNC) were studied. Treatment with anti-delta antibody enhanced both B cell proliferation and plasma cell differentiation, which are T cell-dependent responses. The anti-delta enhancement of plasma cell differentiation, predominantly of IgM plasma cells, was surprising because PWM-responsive subpopulations of B cells have been shown to lack IgD and their plasma cell differentiation is easily and selectively suppressed by anti-mu, -gamma and -alpha antibodies. Treatment of MNC with monoclonal anti-delta antibody enhanced the number of IgM plasma cells induced by PWM stimulation by approximately threefold. The degree of enhancement was dependent upon the concentration of anti-delta antibody, and the F(ab')2 fragments were effective. Maximal enhancement was obtained either when MNC were preincubated with anti-delta antibody for 1 day before PWM stimulation or when anti-delta antibody was added with PWM at the beginning of 7-day cultures. Anti-delta antibody had little or no effect when added 1 to 3 days after the initiation of PWM stimulated cultures. Anti-delta treatment overnight induced a population of small IgM+IgD+ B cells to enlarge and converted them from poor to good PWM responders. The results are discussed in the context of a model which proposed that differentiation of both immature and preactivated mature IgD- cells can be inhibited by signals generated via surface immunoglobulin cross-linkage, whereas this stimulus enhances differentiation of the intermediate IgD+IgM+ B cells.

Antibodies, Anti-Idiotypic↗
PubMed1998

EDF-1, a novel gene product down-regulated in human endothelial cell differentiation.

Endothelial cell differentiation is a crucial step in angiogenesis. Here we report the identification of EDF-1, a novel gene product that is down-regulated when endothelial cells are induced to differentiate in vitro. The cDNA encoding EDF-1 was isolated by RNA fingerprinting from human endothelial cells exposed to human immunodeficiency virus type 1 Tat, a viral protein known to be angiogenic. The deduced amino acid sequence of EDF-1 encodes a basic intracellular protein of 148 amino acids that is homologous to MBF1 (multiprotein-bridging factor 1) of the silkworm Bombyx mori and to H7, which is implicated in the early developmental events of Dictyostelium discoideum. Interestingly, human immunodeficiency virus type 1 Tat, which affects endothelial functions, and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate and culture on fibrin gels, which promote endothelial differentiation in vitro, all down-regulate EDF-1 expression both at the RNA and protein levels. In addition, the inhibition of EDF-1 translation by an antisense anti-EDF-1 construct results in the inhibition of endothelial cell growth and in the transition from a nonpolar cobblestone phenotype to a polar fibroblast-like phenotype. These data suggest that EDF-1 may play a role in the regulation of human endothelial cell differentiation.

Amino Acid Sequence↗
PubMed1995

Interleukin-9 and its receptor: involvement in mast cell differentiation and T cell oncogenesis.

Interleukin-9 (IL-9) is a multifunctional cytokine produced by activated TH2 clones in vitro and during TH2-like T cell responses in vivo. The IL-9 receptor is a member of the hemopoietin receptor superfamily and interacts with the gamma chain of the IL-2 receptor for signal transduction. Various observations indicate that IL-9 is actively involved in mast cell responses by inducing the proliferation and differentiation of these cells. The role of IL-9 in T cell responses is less clear. Although freshly isolated normal T cells do not respond to IL-9, this cytokine induces the proliferation of murine T cell lymphomas in vitro and in vivo overexpression of IL-9 results in the development of thymic lymphomas. In the human, the existence of an IL-9-mediated autocrine loop has been suggested for some malignancies such as Hodgkin's disease. Other potential biological targets for IL-9 include B lymphocytes, hematopoietic progenitors, and immature neuronal cell lines.

Amino Acid Sequence↗
PubMed2000

KRN5500, a novel antitumor agent, induces apoptosis or cell differentiation in HL-60 cells.

BACKGROUND: KRN5500, a derivative of spicamycin, shows antitumor activity against a variety of tumor cell lines. However, the mechanism of cytotoxic action has remained unclear. METHODS: The viability of HL-60 human leukemic cells treated with KRN5500 was studied by the dye exclusion assay. Induction of apoptosis and effects on the cell cycle were investigated by flow cytometry: We measured cellular DNA content after extraction of fragmented DNA, and apoptosis-induced DNA strand breaks. Cell morphology was observed by light microscopy. DNA strand breaks at a nucleosomal unit were analyzed by electrophoresis. RESULTS: Our data demonstrated that KRN5500 caused inhibition of cell growth, and that apoptosis was the mode of cell death. G(1) phase cells were more susceptible to KRN5500 induced apoptosis. In addition, KRN5500 induced cell differentiation at lower concentration. CONCLUSIONS: It is anticipated that KRN5500 will be used clinically as an anti-leukemic agent. Its mechanism of antitumor action is to induce apoptosis or cell differentiation.

Antibiotics, Antineoplastic↗
PubMed1984

Direct effects of a monoclonal B cell differentiation factor and of purified interleukin 1 on B cell differentiation.

We have previously described the presence of factors in mixed lymphocyte culture supernatants that induce activated but not resting human B cells to secrete Ig. In the present study, we describe the effects of a B cell differentiation factor in the supernatant (SN) of a T-T hybridoma (clone 7D5). We find that it induces Ig secretion by human B cells in the absence of T cells or monocytes. It acts only on activated B cells, because small (resting) B cells isolated by centrifugal counterflow elutriation do not respond to it, whereas the same cells do develop into Ig-secreting cells if activated in culture with Staphylococcus aureus Cowan I before exposure to SN 7D5. By using class-specific reagents in enzyme-linked immunosorbent assays, we found SN 7D5 to result in the secretion of significant amounts of IgM, IgG, and IgA. We also studied the effects of highly purified interleukin 1 on this differentiation process. Interleukin 1 by itself failed to induce Ig secretion by activated B cells, and its presence was not required for the induction of Ig secretion by SN 7D5. However, interleukin 1 consistently synergized with SN 7D5 in inducing Ig secretion by purified B cells.

B-Lymphocytes↗
PubMed1995

Vimentin and CP49/filensin form distinct networks in the lens which are independently modulated during lens fibre cell differentiation.

The cells of the eye lens contain the type III intermediate filament protein vimentin, as well as two other intermediate filament proteins, CP49 and filensin. These two proteins appear to be unique to the differentiated lens fibre cell. Immunoblotting and confocal microscopy were used to describe changes which occur in these three intermediate filament proteins and the networks they form during fibre cell differentiation and maturation. The vimentin network was present in both epithelial cells and some fibre cells. Fibre cells were vimentin positive up to a specific point 2-3 mm in from the lens capsule where the vimentin signal was drastically reduced. The CP49/filensin network was not present in the undifferentiated epithelial cells but emerged in the differentiating fibre cells. This latter network exhibited a principally plasma membrane localization in younger fibre cells but became more cytoplasmic in older fibre cells. This change also occurred at a distinct point in fibre cell differentiation, much earlier than the observed loss of the vimentin network. The subcellular changes in the distributions of these cytoskeletal networks were correlated to the loss of the fibre cell nucleus, another feature of fibre cell differentiation. No correlation was found to changes in the vimentin network but nuclear loss did coincide with changes in the CP49/filensin network. Concomitant with nuclear pyknosis, there were also changes in the nuclear lamina as well as infringement of the nuclear compartment by CP49, as shown by confocal microscopy. This study demonstrates vimentin and the CP49/filensin network to be independent in the lens but both networks undergo dramatic changes in subcellular distribution during the differentiation/maturation of the fibre cell. Only changes in the CP49/filensin network can be correlated to nuclear loss. Thus in the lens, unlike mammalian erythropoiesis which is also characterized by nuclear loss, the vimentin network does not appear linked to nuclear retention.

Animals↗
PubMed2000

Adult bone marrow stromal cells differentiate into neural cells in vitro.

Bone marrow stromal cells (BMSC) normally give rise to bone, cartilage, and mesenchymal cells. Recently, bone marrow cells have been shown to have the capacity to differentiate into myocytes, hepatocytes, and glial cells. We now demonstrate that human and mouse BMSC can be induced to differentiate into neural cells under experimental cell culture conditions. BMSC cultured in the presence of EGF or BDNF expressed the protein and mRNA for nestin, a marker of neural precursors. These cultures also expressed glial fibrillary acidic protein (GFAP) and neuron-specific nuclear protein (NeuN). When labeled human or mouse BMSC were cultured with rat fetal mesencephalic or striatal cells, a small proportion of BMSC-derived cells differentiated into neuron-like cells expressing NeuN and glial cells expressing GFAP.

Animals↗
PubMed1988

Tissue interactions and cell differentiation: neurone-sensory cell interaction during otic development.

Statoacoustic ganglion neurones (SAG) are produced by the same group of cells (otic placode) that produce all of the receptor cells that populate the sensory areas of the inner ear. The observation that ingrowth of SAG neurites to presumptive sensory areas of the inner ear preceded cytodifferentiation of those receptor cells suggested a causal relationship. Results from in vivo, in ovo and in vitro studies do not support a causal relationship. These studies support the hypothesis that the programme for labyrinthine sensory cell differentiation is intrinsic and does not require the extrinsic stimulus of neuronal interaction to trigger its expression. In contrast, developing statoacoustic ganglion neurones appear to require a trophic influence that is supplied by either their peripheral or central target tissues for their survival and maturation in vitro. A mechanism for the ingrowth of SAG dendrites to their appropriate target sites within the inner ear proposes that attractant fields produced by areas of differentiating sensory cells act to guide the nerve growth cones of ingrowing SAG neurites to the appropriate tissues. Preliminary results from a heterochronic series of SAG implants to common age otocysts suggest that these SAG neurones are capable of responding to the attractant fields which are produced by presumptive labyrinthine sensory epithelium over an extended period of otic development. Both in ovo and in vitro studies suggest that spatiotemporal patterns of extracellular matrix molecules may be important components of the attractant fields which are produced by the sensory areas of the developing inner ear and may ultimately result in the specificity of their neuronal connections.

Animals↗
PubMed1991

Matrix proteins induce neuroblastoma cell differentiation without altering cell growth.

The maturation of embryonal neural crest cells is thought to be regulated in part by the milieu into which these cells migrate. Neuroblastoma (NB) is a tumor of very early childhood that is thought to arise in association with the arrested differentiation of embryonal neural crest cells. In culture, neuroblastoma tumor cells differentiate in the presence of retinoic acid, which is also known to influence extracellular matrix protein synthesis. We have cultured neuroblastoma cells on laminin (LN) and fibronectin (FN) substrata to examine the role of extracellular matrix in retinoic acid (RA)-induced differentiation of these tumor cells. These proteins caused morphologic changes in NB cells indistinguishable from those caused by RA. Antiserum to each of these proteins blocked the effects induced by the corresponding protein, but neither antiserum affected the action of RA. Despite the induction of a neuronal morphologic change, matrix proteins did not alter the proliferation of NB cells. These results indicate that LN and FN modulate the differentiation of NB cells without inducing growth arrest and that RA-induced differentiation does not require these matrix proteins.

Blotting, Northern↗
PubMedDate not supplied

The cytokine-like action of substance P upon B cell differentiation.

B cells respond to a variety of effector molecules that can induce these cells to differentiate. One such molecule is the neuropeptide, substance P (SP). Previous studies have demonstrated the presence of SP receptors on lymphocytes while limited studies have been able to demonstrate the biological significance of their expression. SP has been shown to enhance IgA and IgM responses by Peyer's patch and splenic B cells. A limitation of these studies was that the direct effect of SP upon B cells was not ascertained, suggesting these B cells were stimulated via alternate mechanisms. To this end, evidence here will be discussed that SP can directly interact with clonal B lymphoma cells and highly purified splenic B cells. The data implicate SP as a late-acting B cell differentiation factor that requires an additional triggering mechanism to initiate the B cell differentiation process.

Amino Acid Sequence↗
PubMed1991

In vitro evaluation of an epoxy resin's cytocompatibility using cell lines and human differentiated cells.

The cytocompatibility of a polyepoxy resin (Elf Aquitaine) has been studied using both cell lines and human differentiated cell cultures. The human models were gingival fibroblasts and bone osteoblasts, while the cell lines were Hela cells and 3T3 Balb/c cells. Basal cytocompatibility was assessed by estimation of the cell proliferation, total cell protein content, cell membrane sub-lysis, and cell attachment and spreading. Specific cytocompatibility concerning human osteoblasts, from both alveolar and trabecular bone, was determined by measuring the intracellular alkaline phosphatase activity. Resin colonization by the cells was studied by both TEM and SEM. The behaviour of the two cell lines reveals a significant level of discrepancy, whereas the behaviour of human cells, whatever the model, is comparable; however, osteoblasts look more sensitive. Moreover, the results show that this epoxy resin exhibits a moderate cytocompatibility which could be the result of the cytotoxicity of early released products, associated with the considerable surface roughness.

Alkaline Phosphatase↗