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SRP169948
Mus musculus
16 Downloadable Samples
NextSeq 500
Description
Microglia 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.
Publication Title
Engrafted parenchymal brain macrophages differ from microglia in transcriptome, chromatin landscape and response to challenge.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
- Illumina HiSeq 4000
Description
Transcription 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.
Publication Title
WNK1 kinase and the termination factor PCF11 connect nuclear mRNA export with transcription.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 19 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative analysis of SF-1 transcription factor dosage impact on genome-wide binding and gene expression regulation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
SF-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.
Publication Title
Integrative analysis of SF-1 transcription factor dosage impact on genome-wide binding and gene expression regulation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 5 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
SF-1 is a nuclear receptor transcription factor playing a key role in adrenogonadal development and in adrenocortical tumorigenesis when overexpressed.
Publication Title
Integrative analysis of SF-1 transcription factor dosage impact on genome-wide binding and gene expression regulation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Saccharomyces cerevisiae
- 7 Downloadable Samples
- Illumina HiSeq 2000, Illumina Genome Analyzer II
Description
Purpose: The goals of this study were to determine whether the spliceosome interacts with non-intronic mRNAs Methods: RNAseq was performed on RNA that immunoprecipitated with the yeast SMD1 protein. Tandem-affinity-purified RNAs were extracted and RNAseq libraries were generated using the EpiCentre ScriptSeq kit (v1). We also performed RNAseq experiments on rRNA depleted total RNA extracted from an exosome mutant (rrp6?), a temperature-sensitive splicing mutant (prp40-1) and a parental strain (BY4741). The rRNA was depleted using the Invitrogen RiboMinus kit, according to manufactureres procedures. The depleted RNA was subsequently treated with Turbo DNAse I (Ambion) and RNAseq libraries were generated using the EpiCentre ScriptSeq kit (v1). Results: The SM RNAseq data identified a number of non-intronic mRNAs that appeard to be bound by the spliceosome. Among these was the BDF2 mRNA, which enocdes for a bromo-domain protein. BDF2 was highly enriched in both SM-IP datasets and was therefore analyzed in more detail. To determine if other non-intronic mRNAs could be regulated by the spliceosome, we analysed the transcriptome in the rrp6?, the prp40-1 and a parental strain. Bioinformatic analysis of these data sets revealed that roughly 1% of the non-intronic mRNAs in yeast could be targeted by the spliceosome. TopHat revealed cannonical splice junctions in roughly 30 non-intronic mRNAs, indicating that these messages are spliced. Conclusions: We demonstrate, for the first time, that the spliceosome can regulate expression of non-intronic mRNAs via one and/or two RNA cleavage events. We refer to this process as Spliceosome Mediated Decay (SMD). Overall design: We report RNAseq data for two SM immunoprecipitation experiments and RNAseq datasets for the parental strain (BY4741), the prp40-1 mutant, and the rrp6? strain.
Publication Title
Spliceosome-mediated decay (SMD) regulates expression of nonintronic genes in budding yeast.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
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.
Publication Title
NR4A orphan nuclear receptors as mediators of CREB-dependent neuroprotection.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 19 Downloadable Samples
- Illumina HiSeq 2000
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. 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).
Publication Title
Nurr1 and Retinoid X Receptor Ligands Stimulate Ret Signaling in Dopamine Neurons and Can Alleviate α-Synuclein Disrupted Gene Expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
B220+GL7+ (GC) and B220+GL7- (non-GC) B cells were sorted from SRBC-immunized mice deficient for Hdac3 and wild type controls. RNA-sequencing revealed an upregulation of critical regulators of B cell differentiation in Hdac3-deleted animals. Overall design: 10 days post-immunization with SRBCs, GC and non-GC B cells were sorted and RNA isolated by Trizol extraction for RNA-sequencing. 2 replicates were sequenced for each condition.
Publication Title
Germinal centre hypoxia and regulation of antibody qualities by a hypoxia response system.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 52 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
We showed that a large number of genes and exons were deregulated in colorectal adenomas in comparison with colorectal normal mucosa.
Publication Title
A gene expression and pre-mRNA splicing signature that marks the adenoma-adenocarcinoma progression in colorectal cancer.
Sample Metadata Fields
Specimen part
View Samples