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Results for “stem cell differentiation”

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PubMed2006

Moclobemide upregulated Bcl-2 expression and induced neural stem cell differentiation into serotoninergic neuron via extracellular-regulated kinase pathway.

1. Moclobemide (MB) is an antidepressant drug that selectively and reversibly inhibits monoamine oxidase-A. Recent studies have revealed that antidepressant drugs possess the characters of potent growth-promoting factors for the development of neurogenesis and improve the survival rate of serotonin (5-hydroxytrytamine; 5-HT) neurons. However, whether MB comprises neuroprotection effects or modulates the proliferation of neural stem cells (NSCs) needs to be elucidated. 2. In this study, firstly, we used the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay to demonstrate that 50 microM MB can increase the cell viability of NSCs. The result of real-time reverse transcription-polymerase chain reaction (RT-PCR) showed that the induction of MB can upregulate the gene expressions of Bcl-2 and Bcl-xL. By using caspases 8 and 3, ELISA and terminal dUTP nick-end labeling (TUNEL) assay, our data further confirmed that 50 microM MB-treated NSCs can prevent FasL-induced apoptosis. 3. The morphological findings also supported the evidence that MB can facilitate the dendritic development and increase the neurite expansion of NSCs. Moreover, we found that MB treatment increased the expression of Bcl-2 in NSCs through activating the extracellular-regulated kinase (ERK) phosphorylation. 4. By using the triple-staining immunofluorescent study, the percentages of serotonin- and MAP-2-positive cells in the day 7 culture of MB-treated NSCs were significantly increased (P<0.01). Furthermore, our data supported that MB treatment increased functional production of serotonin in NSCs via the modulation of ERK1/2. In sum, the study results support that MB can upregulate Bcl-2 expression and induce the differentiation of NSCs into serotoninergic neuron via ERK pathway.

Animals↗
PubMed1999

Regulation of RNA polymerase I transcription in response to F9 embryonal carcinoma stem cell differentiation.

Dramatic changes in the patterns of transcription are a common feature of early development. We have used F9 embryonal carcinoma cells as a model system to study gene regulation during an early stage of murine embryogenesis. We find that transcription by RNA polymerase I decreases when F9 cells differentiate into parietal endoderm. The reduced rate of transcription is associated with a down-regulation of several components of the class I transcription apparatus. The most substantial change involves the essential factor SL1, which is a multisubunit complex that contains the TATA-binding protein and three TATA-binding protein-associated factors (TAFs). The abundance of two of these TAFs, TAFI48 and TAFI95, decreases during F9 cell differentiation. Developmental regulation of a specific class of genes may therefore be achieved through changes in the availability of TAFs.

Animals↗
PubMed1999

The carboxyl-terminal domains of gp130-related cytokine receptors are necessary for suppressing embryonic stem cell differentiation. Involvement of STAT3.

Cell type-specific responses to the leukemia inhibitory factor (LIF)/interleukin 6 cytokine family are mediated by dimerization of the LIF receptor alpha-chain (LIFRalpha) with the signal transducer gp130 or of two gp130 molecules followed by activation of the JAK/STAT and Ras/mitogen-activated protein kinase cascades. In order to dissect the contribution of gp130 and LIFRalpha individually, chimeric molecules consisting of the extracellular domain of the granulocyte colony stimulating factor receptor (GCSF-R) and various mutant forms of the cytoplasmic domains of gp130 or LIFRalpha were expressed in embryonic stem (ES) cells to test for suppression of differentiation, or in a factor-dependent plasma cytoma cell line to assess for induction of proliferation. Carboxyl-terminal domains downstream of the phosphatase (SHP2)-binding sites were dispensable for mitogen-activated protein kinase activation and the transduction of proliferative signals. Moreover, carboxyl-terminal truncation mutants which lacked intact Box 3 homology domains showed decreased STAT3 activation, failed to induce Hck kinase activity and suppress ES cell differentiation. Moreover, STAT3 antisense oligonucleotides impaired LIF-dependent inhibition of differentiation. Substitution of the tyrosine residue within the Box 3 region of the GSCF-R abolished receptor-mediated suppression of differentiation without affecting the transduction of proliferative signals. Thus, distinct cytoplasmic domains within the LIFRalpha, gp130, and GCSF-R transduce proliferative and differentiation suppressing signals.

Antigens, CD↗
PubMed2004

Trophoblast stem cells differentiate in vitro into invasive trophoblast giant cells.

Trophoblast cells are characterized by an invasive behavior into the surrounding uterine tissue. In rodents, an early peri-/endovascular type of invasion exerted by trophoblast giant cells can be distinguished from a late interstitial type carried out by glycogen trophoblast cells. Analysis of the molecular mechanisms of trophoblast invasion has been hampered, however, by the complex temporal and spatial patterns of invasion. We utilized trophoblast stem (TS) cell lines to study trophoblast invasion in vitro and to establish a model that facilitates investigation of this process on the molecular level. Our results showed that trophoblast giant cells that differentiate from TS cells in vitro are capable of penetrating a reconstituted basement membrane matrix. Consequently, invasion rates were increased in various giant cell differentiation-promoting conditions. We also derived TS cell lines that are homozygous for a mutation of the Hand1 transcription factor. The Hand1-/- TS cells showed reduced levels of giant cell differentiation and exhibited an approximately 50% decrease in invasion rates. In summary, trophoblast giant cells that differentiate from TS cells in vitro recapitulate the invasive capacity of normal trophoblast cells in vivo. The TS cell system is a valuable tool to identify and quantitatively study regulators of trophoblast invasion.

Animals↗
PubMed2000

Embryonic stem cells differentiate into oligodendrocytes and myelinate in culture and after spinal cord transplantation.

Demyelination contributes to the loss of function consequent to central nervous system (CNS) injury. Enhanced remyelination through transplantation of myelin-producing cells may offer a pragmatic approach to restoring meaningful neurological function. An unlimited source of cells suitable for such transplantation therapy can be derived from embryonic stem (ES) cells, which are both pluripotent and genetically flexible. In this paper we show that oligodendrocyte cultures can be reliably produced from retinoic acid-induced ES cells and that these oligodendrocytes can myelinate axons in vitro. Methods were further developed for generating highly enriched cultures of oligodendrocytes through an additional culturing step, producing an intermediate "oligosphere" stage. To test whether ES cells can survive, migrate, and differentiate into mature myelin-producing cells in areas of demyelination in the adult CNS, ES cells were transplanted into the dorsal columns of adult rat spinal cord 3 days after chemical demyelination. In the demyelination site, large numbers of ES cells survived and differentiated primarily into mature oligodendrocytes that were capable of myelinating axons. Furthermore, when oligosphere cells were transplanted into the spinal cords of myelin-deficient shiverer (shi/shi) mutant mice, the ES cell-derived oligodendrocytes migrated into the host tissue, produced myelin and myelinated host axons. These studies demonstrate the ability of ES cell-derived oligodendrocytes to myelinate axons in culture and to replace lost myelin in the injured adult CNS. Transplantation of ES cells may be a practical approach to treatment of primary and secondary demyelinating diseases in the adult CNS.

Animals↗
PubMed1994

Retinoic acid-mediated activation of HNF-3 alpha during EC stem cell differentiation.

We present evidence demonstrating that the liver-enriched transcription factor HNF-3 alpha is activated upon retinoic acid-induced differentiation of mouse F9 embryonal carcinoma cells. We have detected increases in the DNA binding activity and mRNA level of HNF-3 alpha. Both are reflections of the actual activation mechanism at the level of transcriptional initiation, which we showed with the help of HNF-3 alpha promoter constructs. Time course studies clearly show that HNF-3 alpha activation is a transient event. Employing Northern blots, HNF-3 alpha mRNA can be detected between 16 and 24 hours post-differentiation, reaches its zenith at approximately 1 day, and then declines to virtually undetectable levels. F9 cells can give rise to three distinct differentiated cell types; visceral endoderm, parietal endoderm, and primitive endoderm. We have clearly shown that HNF-3 alpha stimulation occurs upon primitive endoderm formation. In addition, the transcription factor is also activated during the induction of cell lineages that give rise to parietal and visceral endoderm. HNF-3 alpha stimulation upon visceral endoderm differentiation is accompanied by the activation of HNF-3 target genes such as transthyretin, suggesting that HNF-3 alpha is involved in the developmental activation of this gene. In contrast, HNF-3 alpha target genes in parietal and primitive endoderm have yet to be identified. However, the stimulation of HNF-3 alpha during primitive endoderm formation, which is an extremely early event during murine embryogenesis, points towards a role for the factor in crucial determination processes that occur early during development.

Animals↗
PubMed2006

Cell surface 5T4 antigen is transiently upregulated during early human embryonic stem cell differentiation: effect of 5T4 phenotype on neural lineage formation.

The 5T4 oncofoetal antigen is a cell surface glycoprotein that is transiently expressed during mouse ES cell differentiation and correlates with decreased pluripotency of such cells. We show that 5T4 antigen is transiently unregulated during HES4 and H1 human ES cell differentiation and its expression correlates with loss of the pluripotent markers OCT-4 and Tra-1-60 and upregulation of transcript markers associated with the three primary germ layers. To confirm that absence of cell surface 5T4 antigen represents a pluripotent hES cell phenotype, we performed mechanical transfer of either 5T4-ve or 5T4+ve HES4 colonies identified using live cell staining. 5T4-ve transfers maintained expression of OCT-4 in over 90% of resultant colonies, whereas 5T4+ve transfers exhibited significantly lower numbers of OCT-4-expressing colonies (92 +/- 1.4 vs. 2.9 +/- 2.0%). Interestingly, low cell density 5T4-ve colony transfers exhibited increased numbers of OCT-4-expressing colonies compared to large 5T4-ve transfers (92 +/- 1.4 vs. 63.2 +/- 1.9%). 5T4-ve and 5T4+ve HES4 and H1 ES cell lines expressed markers representative of neuroectoderm lineages, and we assessed the formation of neural lineages from these phenotypes in serum-containing medium and N2B27 medium. Expression of 5T4 was found to be inversely related to the yield of tyrosine-hydroxylase (TH+)-expressing neurons in N2B27 medium, with additional mesoderm and endoderm transcript markers detected. Homogeneous glial cell populations were derived from low cell density 5T4-ve colony transfers cultured in serum-containing medium, with TH+ neuronal formation inhibited in a cell-density-dependent manner. We conclude that the 5T4 antigen is a transient marker of hES cell differentiation and that 5T4 phenotype, colony seeding density and culture conditions significantly influence the maintenance of pluripotent hES cells and their differentiation to neural lineages.

Animals↗
PubMed2005

Identification of cardiac stem cells with FLK1, CD31, and VE-cadherin expression during embryonic stem cell differentiation.

We evaluated the expression of the FLK1, one of the lateral mesoderm early markers where cardiogenesis occurs, to characterize and isolate cardiac stem/progenitor cells from ES cells. Dissociated cells from embryoid bodies (EBs) on day 3, 4, or 5 were collected into two subpopulations with or without FLK1 expression and coculture on OP9 stromal cells was continued to examine whether contracting colonies came out or not. FLK1+ cells from EBs at days 3 and 4 formed spontaneous contracting colonies more efficiently than FLK1- cells on the same days, but not at day 5. Most contracting cardiac colonies derived from FLK1+cells mainly on day 4 were detected on endothelial cells along with hematopoietic cells. Further characterization of cells with these capabilities into three lineages revealed the FLK1+ CD31-VE-cadherin-phenotype. Our findings indicate that FLK1+cells, especially FLK1+ CD31-VE-cadherin-cells, could act as cardiohemangioblasts to form cardiac cells as well as endothelial cells and hematopoietic cells.

Antigens, CD↗
PubMed1980

The critical role of the nucleolus in cell differentiation and stem cell development - an extension of the concept with a look at the mast cell and its possible role in zinc metabolism.

From the assumptions governing the behaviour of primitive cells, a set of corollaries is established and the corollaries are used in coming to an understanding of the growth and differentiation of the pancreas. A case is made out to show that there is a constant replacement of old acini by new throughout the life of the pancreas, and that new acini are derived from primitive cells (fixed reticulum cells) present in the stroma which envelopes the fine ducts. The part played by the mast cells in the process is discussed, and view put forward that circulating thymocytes are mast cell precursors, and that the function of the mast cell is to provide the primitive cells of the pancreas (and the primitive cells of certain other tissues) with Zn in an assimilatable form. The hypothesis is made that Zn can only be assimilated by primitive cells, and, that for organs other than the thymus, it is assimilated in the form of the histamine-Zn complex liberated by the mast cells. The fate of the mast cell is analysed, and the suggestion made that, following degranulation, the mast cell nucleus is transformed into a cell of the eosinophil series. The role of the basophil is also analysed, and the conclusion reached that basophils are mast cells whose development has been modified by plasma.

Basophils↗
PubMed2005

[Human mesenchymal stem cells differentiate into neuron-like cells and show SMN protein expression].

OBJECTIVES: To investigate the mRNA and protein expression of SMN gene in neuron-like cells by inducing MSC to differentiate into neuron-like cells. METHODS: Human MSC (hMSC) were isolated and purified. Human MSC were treated with basic fibroblast growth factor (bFGF) before inducing hMSC to differentiate into neuron-like cells with dimethylsulfoxide (DMSO) and butylated hydroxyanisole (BHA). The expression of NSE, NF, and SMN protein in neuron-like cells were detected by immunohistochemistry. The expression of SMN mRNA were detected with reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Human MSC progressively assumed neuronal morphological characteristics after being induced for 3 hours. Cell bodies had long process contacting with each other. The neuronal marker of NSE and NF was positive in neuron-like cells. Both hMSC and neuron-like cells expressed the mRNA of SMN gene. Compared with hMSC the latter expressed highly the mRNA of SMN gene and it was significance (P < 0.01). SMN protein was only expressed in neuron-like cells. CONCLUSIONS: Human MSC are able to differentiate into neuron-like cells with expressing the neuronal marker. Neuron-like cells can express highly the mRNA of SMN gene and express SMN protein.

Cell Differentiation↗
PubMed1980

Promotion of hematopoietic stem cell differentiation in vitro by a soluble mediator, allogeneic effect factor.

This study was designed to investigate the effects of allogenic effect factor (AEF), a soluble mediator derived from short-term mixed lymphocyte cultures (MLC) of in vitro alloantigen-primed T cells, on cultures of murine bone marrow cells. Cultures established under suboptimal conditions namely, in the absence of a pre-established adherent cell layer as required in conventional Dexter-type cultures--declined and lost their stem cell activity rapidly. In contrast, supplementation of these cultures, at initiation and thereafter, with AEF, but not with T cell growth factor (TCGF), induced cell growth and proliferation for several weeks. Such AEF-supplemented cultures exhibited cellular heterogeneity and stem cell activity for significantly longer periods than the control cultures. Even in conventional Dexter cultures, established under optimal conditions, AEF had a beneficial effect on cellular growth and proliferation and myeloid progenitor cell (CFU-C) activity. Furthermore, cell capable of synergizing with suboptimal numbers of mature T cells in con A-induced mitogenic responses, shown by others to be pre-T cells, were detected in the AEF-supplemented cultures for several weeks.

Animals↗