ES cell-derived neurons of forebrain identity were isolated by magnetic sorting, cultured for 7 days and transduced with either Nurr1 or eGFP lentivirus. After an additional 12 h in culture, mRNA was isolated and subjected to microarray analysis.
NR4A orphan nuclear receptors as mediators of CREB-dependent neuroprotection.
Specimen part
View SamplesWe 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. Overall design: Comparison of 3 Synuclein samples to 5 controls (RFP), Comparison of 3 Synuclein + Nurr1 samples to 5 controls (RFP), Comparison of 3 Bexarotene samples to 3 controls (DMSO), comparison of 1 short hairpin against Nurr1 to 1 control (scrambled).
Nurr1 and Retinoid X Receptor Ligands Stimulate Ret Signaling in Dopamine Neurons and Can Alleviate α-Synuclein Disrupted Gene Expression.
No sample metadata fields
View SamplesNurr1 (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. Overall design: Dopaminergic neurons with or without Nurr1 knocked out. TH-positive neurons were laser capture microdissected from cryostat coronal sections of the midbrain.
Transcription factor Nurr1 maintains fiber integrity and nuclear-encoded mitochondrial gene expression in dopamine neurons.
Specimen part, Subject
View SamplesWe present a microarray analysis of primary mouse astrocytes exposed to HIV-1 in culture. Results are compared with previous genomic studies of HIV-1 effect in human astrocytes and human and macaque brains.
Gene expression profiles of HIV-1-infected glia and brain: toward better understanding of the role of astrocytes in HIV-1-associated neurocognitive disorders.
Specimen part, Treatment
View SamplesTranscription termination and mRNA export from the nucleus are closely regulated and coordinated processes. Nuclear export factors are recruited to actively transcribed genes through their interactions with protein complexes associated with transcription and co-transcriptional pre-mRNA processing. We determine a new role for the kinase WNK1 in the cross-talk of transcription termination and mRNA export. WNK1 was previously attributed a cytoplasmic role as a regulator of ion transport. However, we now show a nuclear function for this kinase where it is required for efficient mRNA export along with the transcription termination factor PCF11. Finally, we identify the phosphorylation of the CID domain of PCF11 as an important step for the release of the mRNA from the transcription locus, thus allowing efficient mRNA export to the cytoplasm. Overall design: RNA from cytoplasmic and nuclear extracts of HeLa cells was obtained, upon depletion of WNK1 kinase or from control cells. Upon pA selection, libraries were generated and sequenced. A duplicate experiment was performed for each sample.
WNK1 kinase and the termination factor PCF11 connect nuclear mRNA export with transcription.
Cell line, Subject
View SamplesMutant embryos lacking maternal and zygotic HOW exhibit defects in mesoderm development. How is an RNA binding protein that regulates the levels of mRNAs by controling RNA metabolism.
Post-transcriptional repression of the Drosophila midkine and pleiotrophin homolog miple by HOW is essential for correct mesoderm spreading.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative analysis of SF-1 transcription factor dosage impact on genome-wide binding and gene expression regulation.
Specimen part, Cell line, Treatment
View SamplesSF-1 is a nuclear receptor transcription factor playing a key role in adrenogonadal development and in adrenocortical tumorigenesis when overexpressed. NRSF/REST is a transcriptional repressor that represses expression of neuronal genes in non-neural tissues. Some data suggest that SF-1 and NRSF/REST can functionally interact in adrenocortical cancer cells.
Integrative analysis of SF-1 transcription factor dosage impact on genome-wide binding and gene expression regulation.
Specimen part, Cell line, Treatment
View SamplesSF-1 is a nuclear receptor transcription factor playing a key role in adrenogonadal development and in adrenocortical tumorigenesis when overexpressed.
Integrative analysis of SF-1 transcription factor dosage impact on genome-wide binding and gene expression regulation.
Specimen part, Cell line, Treatment
View SamplesMicroglia are yolk sac-derived macrophages residing in the parenchyma of brain and spinal cord, where they interact with neurons and other glial cells by constantly probing their surroundings with dynamic extensions. After different conditioning paradigms and bone marrow (BM) or hematopoietic stem cell (HSC) transplantation, graft-derived cells seed the brain and persistently contribute to the parenchymal brain macrophage compartment. Here we establish that graft-derived macrophages acquire, over time, microglia characteristics, including ramified morphology, longevity, radio-resistance and clonal expansion. However, even after prolonged CNS residence, transcriptomes and chromatin accessibility landscapes of engrafted, BM-derived macrophages remain distinct from yolk sac-derived host microglia. Furthermore, engrafted BM-derived cells display discrete responses to peripheral endotoxin challenge, as compared to host microglia. In human HSC transplant recipients, engrafted cells also remain distinct from host microglia, extending our finding to clinical settings. Collectively, our data emphasize the molecular and functional heterogeneity of parenchymal brain macrophages and highlight potential clinical implications for HSC gene therapies aimed to ameliorate lysosomal storage disorders, microgliopathies or general monogenic immuno-deficiencies. Overall design: overall there are 28 samples, from total of 2 experiments. in each experiment there were at least 3 biological repeats (3 individual mice). Sorting of the CD45.1 and CD45.2 populations were performed from the same animal. Animals were either injected with LPS (2.5 mg/kg) or untreated.
Engrafted parenchymal brain macrophages differ from microglia in transcriptome, chromatin landscape and response to challenge.
Specimen part, Cell line, Subject
View Samples