Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The transcription factor nurr1 exerts concentration-dependent effects on target genes mediating distinct biological processes

ABSTRACT: The transcription factor nurr1 plays a pivotal role in the development and maintenance of neurotransmitter phenotype in midbrain dopamine neurons. Conversely, decreased nurr1 expression is associated with a number of dopamine-related CNS disorders, including Parkinson’s disease and drug addiction. In order to better understand the nature of nurr1-responsive genes and their potential roles in dopamine neuron differentiation and survival, we used a neural cellular background in which to generate a number of stable clonal lines with graded nurr1 gene expression that approximated that seen in DA cell-rich human substantia nigra. Gene expression profiling data from these nurr1-expressing clonal lines were validated by quantitative RT-PCR and subjected to bioinformatic analyses. The present study identified a large number of nurr1-responsive genes and demonstrated the potential importance of concentration-dependent nurr1 effects in the differential regulation of distinct nurr1 target genes and biological pathways. These data support the promise of nurr1-based CNS therapeutics for the neuroprotection and/or functional restoration of DA neurons.

ORGANISM(S): Homo sapiens

PROVIDER: GSE33434 | GEO | 2012/01/01

SECONDARY ACCESSION(S): PRJNA148685

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

The transcription factor nurr1 exerts concentration-dependent effects on target genes mediating distinct biological processes

Project description:The transcription factor nurr1 plays a pivotal role in the development and maintenance of neurotransmitter phenotype in midbrain dopamine neurons. Conversely, decreased nurr1 expression is associated with a number of dopamine-related CNS disorders, including Parkinson’s disease and drug addiction. In order to better understand the nature of nurr1-responsive genes and their potential roles in dopamine neuron differentiation and survival, we used a neural cellular background in which to generate a number of stable clonal lines with graded nurr1 gene expression that approximated that seen in DA cell-rich human substantia nigra. Gene expression profiling data from these nurr1-expressing clonal lines were validated by quantitative RT-PCR and subjected to bioinformatic analyses. The present study identified a large number of nurr1-responsive genes and demonstrated the potential importance of concentration-dependent nurr1 effects in the differential regulation of distinct nurr1 target genes and biological pathways. These data support the promise of nurr1-based CNS therapeutics for the neuroprotection and/or functional restoration of DA neurons. Total RNA obtained from nurr1-overexpressing SKNAS neuroblastoma clonal cell lines (SKNAS_E & SKNAS_G) compared to empty vector transfected control (SKNAS_C)

2012-01-01 | E-GEOD-33434 | biostudies-arrayexpress

Comparison of neural stem cell lines overexpressing Nurr1 to clonal controls

Project description:The orphan nuclear receptor Nurr1 has been shown to be critical for the development of ventral midbrain dopaminergic neurons. Consequently, the development of ES cells overexpressing Nurr1 has raised hope for the development of cell replacement therapies for Parkinson's Disease to replace degenerated dopaminergic neurons. However, the molecular consequences of Nurr1 on gene expression in these cells remain unknown. To address this, stable, clonal, c17.2 neural stem cell lines were established that overexpressed the orphan nuclear receptor Nurr1 (clone 42 & clone 48) or parental control cell line (puroB & puroD, respectively). Keywords: genetic modification

2006-05-03 | GSE3571 | GEO

Microarray analysis of Nurr1 and Foxa2 synergisitic effect for DA neuron induction

Project description:Analysis of dopaminergic neuronal gene expression changes by Nurr1 and/or Foxa2 overexpression. Result provides that Foxa2 potentiates Nurr1-induced DA neuronal phenotype gene expression. To identify the syergism of Nurr1 and Foxa2 for developing DA neural precursors, neural precusor cells (NPCs) isolated from embryonic brain were treated control, Nurr1, Foxa2 and Nurr1-Foxa2 retrovirus. After treatment of retroviruses, NPCs were cultrued in N2 media withdrawn mitogen (bFGF, EGF) for differetiation of DA neuron. Total RNA was obtained from NPCs in differentiation day 2.

2014-01-16 | E-GEOD-54086 | biostudies-arrayexpress

Nurr1 and Retinoid X Receptor ligands stimulate Ret signaling in dopamine neurons and can alleviate α-synuclein disrupted gene expression

Project description:We ovexpressed human alpha synuclein alone or together with Nurr1 in mouse primary midbrain cultures and identified the full spectrum of genes whose expression is affected by alpha synuclein, including genes whose expression is normalized after Nurr1 overexpression. Moreover we treated mouse primary midbrain cultures with Bexarotene or short hairpin RNA fro Nurr1, sorted out the dopamine neurons and assessed the effects of Bexarotene and of the Nurr1 downregulation on gene expression.

2015-07-15 | GSE70368 | GEO

Microarray analysis of Nurr1 and Foxa2 synergisitic effect for DA neuron induction

2014-01-16 | GSE54086 | GEO

Transcription profiling of mouse neural stem cell lines overexpressing Nurr1 to clonal controls

2008-06-12 | E-GEOD-3571 | biostudies-arrayexpress

Ascl1, Nurr1 and Lmx1 convert mouse and human fibroblasts into functional dopaminergic neurons without passing through an intermediate precursor state

Project description:Lineage-specific transcription factors, which drive cellular identity during embryogenesis, have been shown to convert cell fate when express ectopically in heterologous cells. Herein, we screened the key molecular factors governing the dopaminergic neuronal specification during brain development for their ability to generate similar neurons directly from mouse and human fibroblasts. Remarkably, we found a minimal set of three factors Mash1, Nurr1 and Lmx1a/b able to elicit such cellular reprogramming. Molecular and transcriptome studies showed reprogrammed DA neurons to faithfully recapitulate gene expression of their brain homolog cells while lacking expression of other catecholaminergic neuronal types. Induced neurons showed spontaneous electrical activity organized in regular spikes consistent with the pacemaker activity featured by brain DA neurons. The three factors were able to elicit DA neuronal conversion in human fibroblasts from prenatal or adult fibroblasts of healthy donors and a Parkinson’s disease patient. Generation of DA induced neurons from somatic cells might have significant implications in studies of neural development, disease in vitro modeling and cell replacement therapies. We infected mouse embryonic fibroblasts (MEFs) isolated from TH-GFP knock-in mice embryos at E14.5, with lentiviruses expressing the three dopaminergic transcription factors Ascl1, Lmx1a and Nurr1. TH-GFP MEFs infected (Ind) by a pool of the three previously mentioned dopaminergic lentiviruses were shifted in a neuronal medium for 12 days and sorted for GFP-positive cells. Thus we extracted mRNA from Ind-GFP-positive cells and compared them to not infetced (NI) cells by means of RNA-microarray analysis.

2011-07-04 | E-GEOD-27174 | biostudies-arrayexpress

Single nucleus RNAseq of midbrain dopaminergic neuronal nuclei isolated by FACS

Project description:While many studies have performed single cell profiling of dopamine (DA) neurons in mice, they have largely been limited by the number of DA neurons captured. Here, we performed single-nucleus RNAseq on DA neurons to refine the DA subtype landscape.

2023-04-26 | GSE222558 | GEO

Ascl1, Nurr1 and Lmx1 convert mouse and human fibroblasts into functional dopaminergic neurons without passing through an intermediate precursor state

2011-07-04 | GSE27174 | GEO

Nurr1 maintains fiber integrity and nuclear-encoded mitochondrial gene expression in dopamine neurons

Project description:Nurr1 (Nr4a2, nuclear receptor subfamily 4 group A member 2) is needed for the development of ventral midbrain dopaminergic neurons, and has been associated with Parkinson's disease. We used mice where the Nurr1 gene is ablated by tamoxifen treatment selectively in dopaminergic neurons. As a control, we used tamoxifen-treated mice where Nurr1 is not ablated. By laser microdissection of neurons selected by their TH1 (Th1l, TH1-like homolog) gene expression, we selected dopaminergic neurons for RNA extraction and high-throughput mRNA sequencing, in order to identify genes regulated by Nurr1. We found the main functional category of Nurr1-regulated genes are the nuclear-encoded mitochondrial genes. Dopaminergic neurons with or without Nurr1 knocked out. TH-positive neurons were laser capture microdissected from cryostat coronal sections of the midbrain.

2013-01-14 | E-GEOD-42912 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data