Rattus norvegicus
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ABSTRACT:
PROVIDER: PRJNA148667 | ENA |
REPOSITORIES: ENA
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Project description:Neuronal differentiation of PC12 cells in response to NGF is a prototypical model in which signal duration determines a biological response. Sustained ERK activity induced by NGF, as compared to transient activity induced by EGF, is critical to the differentiation of these cells. To characterize the transcriptional program activated preferentially by NGF, we compared global gene expression profiles between cells treated with NGF and EGF for 2-4 hrs, when sustained ERK signaling in response to NGF is most distinct from the transient signal elicited by EGF. This analysis identified 69 genes that were preferentially upregulated in response to NGF. PC12 cells that were starved in low serum media for 24 hrs were treated with NGF (50ng/mL) or EGF (25ng/mL) for 2 or 4 hrs, or left untreated. Total RNA for 3 independent biological replicates was extracted and subjected to Affymetrix Rat Gene 1.0ST Arrays. The 69 genes that were preferentially upregulated by NGF compared to EGF met the following criteria: NGF/No treatment log2> 1, FDR p value< 0.01 and NGF/EGF log2> 0.75, FDR p value< 0.01.
2011-11-13 | E-GEOD-33639 | biostudies-arrayexpress
Project description:Neuronal differentiation of PC12 cells in response to NGF is a prototypical model in which signal duration determines a biological response. Sustained ERK activity induced by NGF, as compared to transient activity induced by EGF, is critical to the differentiation of these cells. To characterize the transcriptional program activated preferentially by NGF, we compared global gene expression profiles between cells treated with NGF and EGF for 2-4 hrs, when sustained ERK signaling in response to NGF is most distinct from the transient signal elicited by EGF. This analysis identified 69 genes that were preferentially upregulated in response to NGF.
2011-11-13 | GSE33639 | GEO
Project description:The nerve growth factor NGF has been shown to cause cell fate decisions towards either differentiation or proliferation depending on the relative activity of downstream pERK, pAKT or pJNK signaling. However, how these protein signals are translated into and fed back from transcriptional activity to complete cellular differentiation over a time span of hours to days is still an open question. Using dynamic proteome and transcriptome data from NGF-stimulated PC12 cells over a time span of 24 hours we inferred a dynamic Boolean model capturing the temporal sequence of protein signaling, transcriptional response and subsequent autocrine feedback. Optimal model topology was achieved by introducing multiple time scales for fast cellular signaling and slower gene response and subsequent fitting to the experimental data. The integrated model confirmed the parallel use of MEK/ERK, AKT/PI3K and JNK/JUN for PC12 cell differentiation. Redundancy of cell signaling is demonstrated from the inhibition of the different MAPK pathways. As suggested in silico and confirmed in vitro, differentiation was substantially suppressed under JNK/JUN inhibition, yet delayed only under MEK/ERK inhibition. Most importantly, we found that sustained transcriptional feedback is necessary to induce bistability in the cell fate switch. De novo Gene expression was necessary to activate autocrine feedback that caused integrin signaling to perpetuate the MAPK activity, finally resulting in the expression of late, differentiation related genes. Thus, the cellular decision towards differentiation depends on the establishment of a transcriptome-induced positive feedback between protein signaling and gene expression thereby constituting a robust control between proliferation and differentiation. To eludicate the transcriptome response of PC12 cells time-resolved gene expression data of NGF or EGF simulated PC12 were recorded at t = [0.5h 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 48h] for NGF and at t=[1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h]. Control time points of unstimulated PC12 cells were taken at t=[0h, 2h, 4h, 6h, 8h, 24h, 48h]. Additionally, the MEK-inhibitor UO126 was added together with NGF and the gene response was measured at t=[1h, 2h, 4h, 6h, 8h, 12h, 24h, 48h] and for UO126 alone at t=[1h, 2h, 4h, 8h, 12h, 48h]. Total RNA was isolated, labeled and hybridized to an Illumina ratRef-12 bead array (Illumina, San Diego, CA, USA) according to the manufacturerâ??s protocol.
2016-03-23 | E-GEOD-74327 | biostudies-arrayexpress
Project description:Continuous NGF stimulation induces PC12 cell differentiation; however, it is unclear whether NGF is continuously required for differentiation. We found that discontinuous NGF stimulation, consisting of the first transient stimulation followed by an interval and the second sustained stimulation, similarly induces differentiation. The first stimulation did not induce neurite extension, whereas the second stimulation induced fast neurite extension; therefore, the first stimulation is required as prerequisite conditions. This indicates that the action of NGF can be divided into two processes: the first stimulation-driven latent process and the second stimulation-driven extension process. The latent process appears to require ERK and transcription, but not PI3K, activities, whereas the extension-process requires ERK and PI3K, but not transcription, activities. We also found that NGF in the first stimulation can be replaced by PACAP, but not by insulin, EGF, bFGF or forskolin, whereas NGF in the second stimulation cannot be replaced by any of these stimulants. These findings allowed us to identify potential genes specifically involved in the latent process, rather than in other processes. These results demonstrate that NGF induces differentiation of PC12 cells via mechanically distinct processes: the ERK-driven and transcription-dependent latent process; and the ERK- and PI3K-driven, and transcription-independent extension process.
2010-02-13 | GSE18016 | GEO
Project description:The nerve growth factor NGF has been shown to cause cell fate decisions towards either differentiation or proliferation depending on the relative activity of downstream pERK, pAKT or pJNK signaling. However, how these protein signals are translated into and fed back from transcriptional activity to complete cellular differentiation over a time span of hours to days is still an open question. Using dynamic proteome and transcriptome data from NGF-stimulated PC12 cells over a time span of 24 hours we inferred a dynamic Boolean model capturing the temporal sequence of protein signaling, transcriptional response and subsequent autocrine feedback. Optimal model topology was achieved by introducing multiple time scales for fast cellular signaling and slower gene response and subsequent fitting to the experimental data. The integrated model confirmed the parallel use of MEK/ERK, AKT/PI3K and JNK/JUN for PC12 cell differentiation. Redundancy of cell signaling is demonstrated from the inhibition of the different MAPK pathways. As suggested in silico and confirmed in vitro, differentiation was substantially suppressed under JNK/JUN inhibition, yet delayed only under MEK/ERK inhibition. Most importantly, we found that sustained transcriptional feedback is necessary to induce bistability in the cell fate switch. De novo Gene expression was necessary to activate autocrine feedback that caused integrin signaling to perpetuate the MAPK activity, finally resulting in the expression of late, differentiation related genes. Thus, the cellular decision towards differentiation depends on the establishment of a transcriptome-induced positive feedback between protein signaling and gene expression thereby constituting a robust control between proliferation and differentiation.
2016-03-23 | GSE74327 | GEO
Project description:We analyzed the comprehensive gene expression changes by nerve growth factor (NGF) in PC12 cells using Agilent microarrays. The genes of 1920 NGF treated were up-regulated and 2670 genes were down-regulated significantly compared with the control group. The expression level of genes involved in cell structure and proteolysis were up-regulated. On the other hand, the genes of cell cycle and some metabolism were rather down-regulated. Therefore, it is suggested that it is necessary to stop the cell cycle and down-regulate metabolism to neurite outgrowth. Gene regulation associated with the differentiation program in PC12 cells still needs to be elucidated. We analyzed the genes expression with Agilent microarrays after 6 hours of NGF treatment by the one-color method, and found 2099 genes were up-regulated and 2781 genes were down-regulated.
2012-04-24 | E-GEOD-37564 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are small non-coding RNAs that control protein expression through translational inhibition or mRNA degradation. MiRNAs have been implicated in diverse biological processes such as development, proliferation, apoptosis and differentiation. Upon treatment with nerve growth factor (NGF), rat pheochromocytoma PC12 cells elicit neurite outgrowth and differentiae into neuron-like cells. NGF plays a critical role not only in neuronal differentiation but also in protection against apoptosis. In an attempt to identify NGF-regulated miRNAs in PC12 cells, we performed miRNA microarray analysis using total RNAs harvested from cells treated with NGF. In response to NGF treatment, expression of 8 and 12 miRNAs were up- and down-regulated, respectively. Quantitative RT-PCR analysis confirmed increased expression of miR-221, miR-181a* and miR-326, and decreased expression of miR-143, miR-210 and miR-532-3p after NGF treatment, among which miR-221 was drastically up-regulated. Overexpression of miR-221 induced neurite outgrowth of PC12 cells in the absence of NGF treatment, and also enhanced neurite outgrowth caused by low-dose NGF. More importantly, knockdown of miR-221 by antagomir attenuated NGF-mediated neurite outgrowth. Finally, miR-221 decreased expression of Foxo3a and Apaf-1, both of which are involved in apoptosis in PC12 cells. Our results indicate that miR-221 plays a critical role for neuronal differentiation as well as protection against apoptosis in PC12 cells.
2012-05-16 | GSE32122 | GEO
Project description:This a model from the article:
Prediction and validation of the distinct dynamics of transient and sustained ERK activation.
Sasagawa S, Ozaki Y, Fujita K, Kuroda S
Nat. Cell Biol.[2005 Apr; Volume: 7 (Issue: 4 )]: 365-73
15793571,
Abstract:
To elucidate the hidden dynamics of extracellular-signal-regulated kinase (ERK) signalling networks, we developed a simulation model of ERK signalling networks by constraining in silico dynamics based on in vivo dynamics in PC12 cells. We predicted and validated that transient ERK activation depends on rapid increases of epidermal growth factor and nerve growth factor (NGF) but not on their final concentrations, whereas sustained ERK activation depends on the final concentration of NGF but not on the temporal rate of increase. These ERK dynamics depend on Ras and Rap1 dynamics, the inactivation processes of which are growth-factor-dependent and -independent, respectively. Therefore, the Ras and Rap1 systems capture the temporal rate and concentration of growth factors, and encode these distinct physical properties into transient and sustained ERK activation, respectively.
Dynamics of active Ras, active Rap1 and phosphorylated ERK were correctly reproduced with CellDesigner 3.0
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2012 The BioModels.net Team.
For more information see the terms of use.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2024-09-02 | BIOMD0000000049 | BioModels
Project description:MicroRNAs (miRNAs) are small non-coding RNAs that control protein expression through translational inhibition or mRNA degradation. MiRNAs have been implicated in diverse biological processes such as development, proliferation, apoptosis and differentiation. Upon treatment with nerve growth factor (NGF), rat pheochromocytoma PC12 cells elicit neurite outgrowth and differentiae into neuron-like cells. NGF plays a critical role not only in neuronal differentiation but also in protection against apoptosis. In an attempt to identify NGF-regulated miRNAs in PC12 cells, we performed miRNAM-cM-^@M-^@microarray analysis using total RNAs harvested from cells treated with NGF. In response to NGF treatment, expression of 8 and 12 miRNAs were up- and down-regulated, respectively. Quantitative RT-PCR analysis confirmed increased expression of miR-221, miR-181a* and miR-326, and decreased expression of miR-143, miR-210 and miR-532-3p after NGF treatment, among which miR-221 was drastically up-regulated. Overexpression of miR-221 induced neurite outgrowth of PC12 cells in the absence of NGF treatment, and also enhanced neurite outgrowth caused by low-dose NGF. More importantly, knockdown of miR-221 by antagomir attenuated NGF-mediated neurite outgrowth. Finally, miR-221 decreased expression of Foxo3a and Apaf-1, both of which are involved in apoptosis in PC12 cells. Our results indicate that miR-221 plays a critical role for neuronal differentiation as well as protection against apoptosis in PC12 cells. NGF induced miRNAs expression in rat pheochromocytoma PC12 cells was measured in cells treated with 100 ng/ml NGF for 0, 12, 24 and 48 hr.
2012-05-15 | E-GEOD-32122 | biostudies-arrayexpress
Project description:miRNA profiling of PC12 rat pheochromocytoma cells during NGF-induced differentiation and apoptosis of differentiated cells after 24h of NGF deprivation. miRNA expression in differentiating and deprivated cells was compared to untreated and terminally differentiated PC12 cells respectivelly.
2013-05-11 | GSE46827 | GEO