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GSE11582
Pan troglodytes, Homo sapiens
355 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Lymphoblastoid cell lines (LCLs), originally collected as renewable sources of DNA, are now being used as a model system to study genotype-phenotype relationships in human cells. These cell lines have been used to search for genetic variants that are associated with drug response as well as with more basic cellular traits such as RNA levels. In setting out to extend such studies by searching for genetic variants contributing to drug response, we observed that phenotypes in LCLs were, in our lab and others, significantly affected by experimental confounders (i.e. in vitro growth rate, metabolic state, and relative levels of the Epstein-Barr virus used to transform the cells). As we did not find any SNPs associated with genome-wide significance to drug response, we evaluated whether incorporating RNA expression levels (and eQTLs) in the analysis could increase power to detect such effects. As previously shown, cis-acting eQTLs were detectable for a sizeable fraction of RNAs and baseline levels of many RNAs predicted response to several drugs. However, we found only limited evidence that SNPs influenced drug response through their effect on expression of RNA. Efforts to use LCLs to map genes underlying cellular traits will require great care to control experimental confounders, unbiased methods for integrating and interpreting such multi-dimensional data, and much larger sample sizes than have been applied to date.
Publication Title
Genetic analysis of human traits in vitro: drug response and gene expression in lymphoblastoid cell lines.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 4 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Heart formation requires input from two populations of progenitor cells - the first and second heart fields - that differentiate at distinct times and create different cardiac components. The cardiac outflow tract (OFT) is built through recruitment of late-differentiating, second heart field (SHF) -derived cardiomyocytes to the arterial pole of the heart. Mechanisms responsible for selection of an appropriate number of OFT cells from the SHF remain unclear, although several lines of evidence emphasize the importance of FGF signaling in promoting this process. Here, we examine the impact of inhibition of FGF signaling on cardiac transcription profiles in an effort to identify genes operating downstream of FGF during OFT development.
Publication Title
Cadm4 restricts the production of cardiac outflow tract progenitor cells.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 6 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Heart formation requires the fusion of bilateral cardiomyocyte populations as they move toward the embryonic midline. The bHLH transcription factor Hand2 is essential for cardiac fusion; however, the effector genes that execute this function of Hand2 are unknown. Here, we provide the first evidence for a downstream component of the Hand2 pathway that mediates cardiac morphogenesis. Although hand2 is expressed in cardiomyocytes, mosaic analysis demonstrates that hand2 plays a non-autonomous role in regulating cardiomyocyte movement. Gene expression profiles reveal heightened expression of fibronectin 1 (fn1) in hand2 mutant embryos. Reciprocally, overexpression of hand2 leads to decreased Fibronectin levels. Furthermore, reduction of fn1 function enables rescue of cardiac fusion in hand2 mutants: bilateral cardiomyocyte populations merge and exhibit improved tissue architecture, albeit without major changes in apicobasal polarity. Together, our data provide a novel example of a tissue creating a favorable environment for its morphogenesis: the Hand2 pathway establishes an appropriate environment for cardiac fusion through negative modulation of Fn1 levels.
Publication Title
Hand2 ensures an appropriate environment for cardiac fusion by limiting Fibronectin function.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
MiR-142 is upregulated in neurons in HIV and SIV encephalitis. We have created stable clones of the BE(2)M17 human neuroblastoma cell line overexpressing miR-142.
Publication Title
MicroRNA-142 reduces monoamine oxidase A expression and activity in neuronal cells by downregulating SIRT1.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 320 Downloadable Samples
NextSeq 500
Description
Certain neuron types fire spontaneously at high rates, an ability that is crucial for their function in brain circuits. The spontaneously active GABAergic neurons of the substantia nigra pars reticulata (SNr), a major output of the basal ganglia, provide tonic inhibition of downstream brain areas. A depolarizing "leak" current supports this firing pattern, but its molecular basis remains poorly understood. To understand how SNr neurons maintain tonic activity, we used single-cell RNA sequencing to determine the transcriptome of individual SNr neurons. We discovered that SNr neurons express the sodium leak current, NaLCN and that SNr neurons lacking NaLCN have impaired spontaneous firing. Overall design: RNA sequencing profiles from 87 GFP-positive GABAergic SNr neurons and 9 GFP-negative SNr cells were carried out. However only 80 samples that passed initial quality control and that were included in the data processing are represented in this record.
Publication Title
The leak channel NALCN controls tonic firing and glycolytic sensitivity of substantia nigra pars reticulata neurons.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Formation of the complex vertebrate nervous system begins when pluripotent cells of the early embryo are directed to acquire a neural fate. Although cell intrinsic controls play an important role in this process, the molecular nature of this regulation is not well defined. Here we assessed the role for Geminin, a nuclear protein expressed in embryonic cells, in neural fate acquisition from mouse embryonic stem (ES) cells. While Geminin knockdown does not affect the ability of ES cells to maintain or exit pluripotency, we found that it significantly impairs their ability to acquire a neural fate. Conversely, Geminin overexpression promotes neural gene expression, even in the presence of growth factor signaling that antagonizes neural transcriptional responses. These data demonstrate that Geminins activity contributes to mammalian neural cell fate acquisition. We investigated the mechanistic basis of this phenomenon and found that Geminin maintains a hyperacetylated and open chromatin conformation at neural genes. Interestingly, recombinant Geminin protein also rapidly alters chromatin acetylation and accessibility even when Geminin is combined with nuclear extract and chromatin in vitro. These findings define a novel activity for Geminin in regulation of chromatin structure. Together, these data support a role for Geminin as a cell intrinsic regulator of neural fate acquisition that promotes expression of neural genes by regulating chromatin accessibility and histone acetylation.
Publication Title
Geminin promotes neural fate acquisition of embryonic stem cells by maintaining chromatin in an accessible and hyperacetylated state.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus, Xenopus laevis
- 6 Downloadable Samples
- Affymetrix Xenopus laevis Genome Array (xenopuslaevis)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Geminin regulates the transcriptional and epigenetic status of neuronal fate-promoting genes during mammalian neurogenesis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Xenopus laevis
- 6 Downloadable Samples
- Affymetrix Xenopus laevis Genome Array (xenopuslaevis)
Description
Transcriptional targets of neurogenin (Ngnr1) were identified by over-expression of an inducible form of neurogenin in Xenopus ectodermal explants. The effects of co-expressing the nucleoprotein geminin on Ngnr1-dependent target gene transactivation were defined.
Publication Title
Geminin regulates the transcriptional and epigenetic status of neuronal fate-promoting genes during mammalian neurogenesis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Regulating the transition from lineage-restricted progenitors to terminally differentiated cells is a central aspect of nervous system development. Here, we investigated the role of the nucleoprotein Geminin in regulating neurogenesis at a mechanistic level during both Xenopus primary neurogenesis and mammalian neuronal differentiation in vitro. The latter work utilized both neural cells derived from embryonic stem and embryonal carcinoma cells in vitro and neural stem cells from mouse forebrain. In all of these contexts, Geminin antagonized the ability of neural bHLH transcription factors to activate transcriptional programs promoting neurogenesis. Furthermore, Geminin promoted a bivalent chromatin state, characterized by the presence of both activating and repressive histone modifications, at genes encoding transcription factors that promote neurogenesis. This epigenetic state restrains the expression of genes that regulate commitment of undifferentiated stem and neuronal precursor cells to neuronal lineages. Geminin is highly expressed in undifferentiated neuronal precursor cells but is downregulated prior to differentiation. Therefore, these data support a model whereby Geminin promotes the neuronal precursor cell state by modulating both the epigenetic status and expression of genes encoding neurogenesis-promoting factors. Additional developmental signals acting in these cells can then control their transition toward terminal neuronal or glial differentiation during mammalian neurogenesis. Overall design: A mouse embryonic stem (ES) cell line for inducible knockdown of the small nucleoprotein Geminin was utilized. ES cells were used to generate neural precursor cells by monolayer culture in N2B27 media for 5 days, and doxycycline-inducible knockdown of Geminin was performed from day 3. Changes in gene expression resulting from Geminin knockdown were assessed by RNA sequencing. Three experimental replicates were generated for Geminin knockdown (plus Dox) with a corresponding no-Dox control. These were subjected to sequencing, and data were analyzed using TopHat and Cufflinks/Cuffdiff. Transcripts were considered as differentially expressed upon Gem knockdown if data met statistical significance cutoffs in Cuffdiff (sufficient sequence alignments were obtained for analysis and transcript had significant change in FPKM value (normalized transcript abundance; fragments per kb of exon per million fragments mapped) between the no Dox and plus Dox sample pairs) in at least two of the three replicates.
Publication Title
Geminin regulates the transcriptional and epigenetic status of neuronal fate-promoting genes during mammalian neurogenesis.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Histone-fold domain protein NF-Y promotes chromatin accessibility for cell type-specific master transcription factors.
Sample Metadata Fields
Specimen part
View Samples