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Differentiation Inducers (differentiation + inducer)
Selected AbstractsMorphogens and cell survival during developmentDEVELOPMENTAL NEUROBIOLOGY, Issue 4 2005Patrick Mehlen Abstract The notion of "morphogens" is an important one in developmental biology. By definition, a morphogen is a molecule that emanates from a specific set of cells that is present in a concentration gradient and that specifies the fate of each cell along this gradient. The strongest candidate morphogens are members of the transforming growth factor-, (TGF-,), Hedgehog (Hh), and Wnt families. While these morphogens have been extensively described as differentiation inducers, some reports also suggest their possible involvement in cell death and cell survival. It is frequently speculated that the cell death induction that is found associated with experimental removal of morphogens is the manifestation of abnormal differentiation signals. However, several recent reports have raised controversy about this death by default, suggesting that cell death regulation is an active process for shaping tissues and organs. In this review, we will present morphogens, with a specific emphasis on Sonic Hedgehog, a mammalian member of the Hh family, not as a positive regulators of cell differentiation but as key regulators of cell survival. © 2005 Wiley Periodicals, Inc. J Neurobiol 64: 357,366, 2005 [source] Group III metabotropic glutamate receptor activation suppresses self-replication of undifferentiated neocortical progenitor cellsJOURNAL OF NEUROCHEMISTRY, Issue 5 2008Noritaka Nakamichi§ Abstract We evaluated the possible functional expression of metabotropic glutamate receptors (mGluRs) by neural progenitors from embryonic mouse neocortex. Constitutive expression was seen with group I, II, and III mGluRs in undifferentiated cells and neurospheres formed by clustered cells during culture with epidermal growth factor. The group III mGluR agonist, l -2-amino-4-phosphonobutyrate, drastically reduced proliferation activity at 1,100 ,M without inducing cell death, with group I and group II mGluR agonists being ineffective, in these neurospheres. Both forskolin and a group III mGluR antagonist significantly increased the proliferation alone, but significantly prevented the suppression by l -2-amino-4-phosphonobutyrate. Activation of group III mGluR significantly decreased mRNA expression of the cell cycle regulator cyclinD1, in addition to inhibiting the transactivation mediated by cAMP of cyclinD1 gene in the pluripotent P19 progenitor cells. Prior activation of group III mGluR led to a significant decrease in the number of cells immunoreactive for a neuronal marker, with an increase in that for an astroglial marker irrespective of differentiation inducers. These results suggest that group III mGluR may be functionally expressed to suppress self-renewal capacity through a mechanism related to cAMP formation with promotion of subsequent differentiation into astroglial lineage in neural progenitors. [source] Possible promotion of neuronal differentiation in fetal rat brain neural progenitor cells after sustained exposure to static magnetismJOURNAL OF NEUROSCIENCE RESEARCH, Issue 11 2009Noritaka Nakamichi Abstract We have previously shown significant potentiation of Ca2+ influx mediated by N-methyl- D -aspartate receptors, along with decreased microtubules-associated protein-2 (MAP2) expression, in hippocampal neurons cultured under static magnetism without cell death. In this study, we investigated the effects of static magnetism on the functionality of neural progenitor cells endowed to proliferate for self-replication and differentiate into neuronal, astroglial, and oligodendroglial lineages. Neural progenitor cells were isolated from embryonic rat neocortex and hippocampus, followed by culture under static magnetism at 100 mT and subsequent determination of the number of cells immunoreactive for a marker protein of particular progeny lineages. Static magnetism not only significantly decreased proliferation of neural progenitor cells without affecting cell viability, but also promoted differentiation into cells immunoreactive for MAP2 with a concomitant decrease in that for an astroglial marker, irrespective of the presence of differentiation inducers. In neural progenitors cultured under static magnetism, a significant increase was seen in mRNA expression of several activator-type proneural genes, such as Mash1, Math1, and Math3, together with decreased mRNA expression of the repressor type Hes5. These results suggest that sustained static magnetism could suppress proliferation for self-renewal and facilitate differentiation into neurons through promoted expression of activator-type proneural genes by progenitor cells in fetal rat brain. © 2009 Wiley-Liss, Inc. [source] Therapeutic strategy using phenotypic modulation of cancer cells by differentiation-inducing agentsCANCER SCIENCE, Issue 11 2007Yoshio Honma A low concentration of differentiation inducers greatly enhances the in vitro and in vivo antiproliferative effects of interferon (IFN), in several human cancer cells. Among the differentiation inducers tested, the sensitivity of cancer cells to IFN, was most strongly affected by cotylenin A. Cotylenin A, which is a novel fusicoccane diterpene glycoside with a complex sugar moiety, affected the differentiation of leukemia cells that were freshly isolated from acute myelogenous leukemia patients in primary culture. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptor DR5 were early genes induced by the combination of cotylenin A and IFN, in carcinoma cells. Neutralizing antibody to TRAIL inhibited apoptosis, suggesting that cotylenin A and IFN, cooperatively induced apoptosis through the TRAIL signaling system. Combined treatment preferentially induced apoptosis in human lung cancer cells while sparing normal lung epithelial cells. In an analysis of various cancer cell lines, ovarian cancer cells were highly sensitive to combined treatment with cotylenin A and IFN, in terms of the inhibition of cell growth. This treatment was also effective toward ovarian cancer cells that were refractory to cisplatin, and significantly inhibited the growth of ovarian cancer cells as xenografts without apparent adverse effects. Ovarian cancer cells from patients were also sensitive to the combined treatment in primary cultures. Combined treatment with cotylenin A and IFN, may have therapeutic value in treating human cancers including ovarian cancer. (Cancer Sci 2007; 98: 1643,1651) [source] | ||||||||||