scholarly journals Boolean Modeling Reveals the Necessity of Transcriptional Regulation for Bistability in PC12 Cell Differentiation

2016 ◽  
Vol 7 ◽  
Author(s):  
Barbara Offermann ◽  
Steffen Knauer ◽  
Amit Singh ◽  
María L. Fernández-Cachón ◽  
Martin Klose ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Cell Differentiation ◽  
Pc12 Cell ◽  
Boolean Modeling

scholarly journals METTL3-dependent m6A modification programs T follicular helper cell differentiation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yingpeng Yao ◽  
Ying Yang ◽  
Wenhui Guo ◽  
Lifan Xu ◽  
Menghao You ◽  
...  
Keyword(s):  
T Cells ◽  
Transcriptional Regulation ◽  
Cell Differentiation ◽  
Ectopic Expression ◽  
Signature Genes ◽  
Follicular Helper ◽  
Conditional Deletion ◽  
A Cell ◽  
A Site ◽  
Post Transcriptional Regulation

AbstractT follicular helper (TFH) cells are specialized effector CD4+ T cells critical to humoral immunity. Whether post-transcriptional regulation has a function in TFH cells is unknown. Here, we show conditional deletion of METTL3 (a methyltransferase catalyzing mRNA N6-methyladenosine (m6A) modification) in CD4+ T cells impairs TFH differentiation and germinal center responses in a cell-intrinsic manner in mice. METTL3 is necessary for expression of important TFH signature genes, including Tcf7, Bcl6, Icos and Cxcr5 and these effects depend on intact methyltransferase activity. m6A-miCLIP-seq shows the 3′ UTR of Tcf7 mRNA is subjected to METTL3-dependent m6A modification. Loss of METTL3 or mutation of the Tcf7 3′ UTR m6A site results in accelerated decay of Tcf7 transcripts. Importantly, ectopic expression of TCF-1 (encoded by Tcf7) rectifies TFH defects owing to METTL3 deficiency. Our findings indicate that METTL3 stabilizes Tcf7 transcripts via m6A modification to ensure activation of a TFH transcriptional program, indicating a pivotal function of post-transcriptional regulation in promoting TFH cell differentiation.

Mechanisms of Manganese-Induced Rat Pheochromocytoma (PC12) Cell Death and Cell Differentiation

2002 ◽  
Vol 23 (2) ◽  
pp. 147-157 ◽  
Author(s):  
Jerome A. Roth ◽  
Craig Horbinski ◽  
Dennis Higgins ◽  
Pamela Lein ◽  
Michael D. Garrick
Keyword(s):  
Cell Death ◽  
Cell Differentiation ◽  
Pc12 Cell ◽  
Pheochromocytoma Pc12

Microtubule-associated protein 1B phosphorylation by glycogen synthase kinase 3β is induced during PC12 cell differentiation

2001 ◽  
Vol 114 (23) ◽  
pp. 4273-4284 ◽  
Author(s):  
Robert G. Goold ◽  
Phillip R. Gordon-Weeks
Keyword(s):  
Cell Differentiation ◽  
Pc12 Cell ◽  
Glycogen Synthase ◽  
Axon Outgrowth ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β ◽  
Cell Extracts ◽  
Neurite Formation ◽  
Reduced Mobility

In recent studies we have demonstrated that glycogen synthase kinase 3β (GSK3β) and its substrate microtubule-associated protein 1B (MAP1B) regulate the microtubule cytoskeleton during axon outgrowth. To further examine the role GSK3β plays in axon outgrowth we investigated the expression of GSK3β and its activity towards MAP1B during nerve growth factor (NGF)-stimulated PC12 cell differentiation. Levels of GSK3β expression increase relatively little during the course of differentiation. However, the expression of a novel GSK3β isoform characterised by a reduced mobility on SDS gels is induced by NGF. Expression of this isoform and the GSK3β-phosphorylated isoform of MAP1B (MAP1B-P) are induced in parallel in response to NGF. This increase lags behind initial neurite formation and the expression of MAP1B in these cells by about two days and coincides with a period when the majority of cells are extending existing neurites. MAP1B and GSK3β are expressed throughout the PC12 cell but MAP1B-P expression is restricted to the growth cones and neurites. Consistent with these observations, we find that neurite extension is more sensitive to the GSK3 inhibitor Li+ than neurite formation and that this correlates with an inhibition of MAP1B phosphorylation. Additionally, GSK3β from PC12 cells not exposed to NGF can not phosphorylate MAP1B in vitro. However, a soluble factor in differentiated PC12 cell extracts depleted of GSK3β can activate MAP1B phosphorylation from undifferentiated cell extracts otherwise devoid of kinase activity. These experiments provide evidence for an NGF-mediated regulation of MAP1B phosphorylation in growing neurites by the induction of a novel isoform of GSK3β.

scholarly journals Mitogen-activated protein kinase activation is insufficient for growth factor receptor-mediated PC12 cell differentiation.

1995 ◽  
Vol 15 (7) ◽  
pp. 3644-3653 ◽  
Author(s):  
R R Vaillancourt ◽  
L E Heasley ◽  
J Zamarripa ◽  
B Storey ◽  
M Valius ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Growth Factor ◽  
Map Kinase ◽  
Pc12 Cells ◽  
Pc12 Cell ◽  
Growth Factor Receptor ◽  
Receptor Activation ◽  
Mitogen Activated Protein ◽  
Map Kinase Pathway ◽  
Kinase Pathway

When expressed in PC12 cells, the platelet-derived growth factor beta receptor (beta PDGF-R) mediates cell differentiation. Mutational analysis of the beta PDGF-R indicated that persistent receptor stimulation of the Ras/Raf/mitogen-activated protein (MAP) kinase pathway alone was insufficient to sustain PC12 cell differentiation. PDGF receptor activation of signal pathways involving p60c-src or the persistent regulation of phospholipase C gamma was required for PC12 cell differentiation. beta PDGF-R regulation of phosphatidylinositol 3-kinase, the GTPase-activating protein of Ras, and the tyrosine phosphatase, Syp, was not required for PC12 cell differentiation. In contrast to overexpression of oncoproteins involved in regulating the MAP kinase pathway, growth factor receptor-mediated differentiation of PC12 cells requires the integration of other signals with the Ras/Raf/MAP kinase pathway.

Transcriptional regulation of peripheral glial cell differentiation in the embryonic nervous system of drosophila

Glia ◽  
2011 ◽  
Vol 59 (9) ◽  
pp. 1264-1272 ◽  
Author(s):  
Imke Schmidt ◽  
Sigrídur Rut Franzdóttir ◽  
Gundula Edenfeld ◽  
Floriano Rodrigues ◽  
Ariane Zierau ◽  
...  
Keyword(s):  
Nervous System ◽  
Transcriptional Regulation ◽  
Cell Differentiation ◽  
Glial Cell ◽  
Embryonic Nervous System

The T. cruzi trans-sialidase induces PC12 cell differentiation via MAPK/ERK pathway

Neuroreport ◽  
2001 ◽  
Vol 12 (17) ◽  
pp. 3715-3718 ◽  
Author(s):  
Marina V. Chuenkova ◽  
Miercio A. Pereira
Keyword(s):  
Cell Differentiation ◽  
Pc12 Cell ◽  
Erk Pathway
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