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Mus musculus
204 Downloadable Samples
Illumina HiSeq 2000
Description
Cortical GABAergic interneurons constitute a highly diverse population of inhibitory neurons that are key regulators of cortical microcircuit function. An important and heterogeneous group of cortical interneurons specifically expresses the serotonin receptor 3A (5-HT3AR) but how this diversity emerges during development is poorly understood. Here we use single-cell transcriptomics to identify gene expression patterns operating in Htr3a-GFP+ interneurons during early steps of cortical circuit assembly. We identify 3 main molecular types of Htr3a-GFP+ interneurons, each displaying distinct developmental dynamics of gene expression. The transcription factor Meis2 is specifically enriched in a type of Htr3a-GFP+ interneurons spatially confined to the cortical white matter. These MEIS2 expressing interneurons appear to originate from a restricted region located at the embryonic pallial-subpallial boundary. Overall, this study identifies MEIS2 as a subclass-specific marker for 5-HT3AR-containing interstitial interneurons and demonstrates that the transcriptional and anatomical parcellation of cortical interneurons is developmentally coupled. Overall design: Single cell transcriptomics of cortical interneurons FACS sorted according to GFP-Htr3a+. Acquired from mouse brains of 3 different developmental ages: E18, P2, P5
Publication Title
Transcriptomic and anatomic parcellation of 5-HT<sub>3A</sub>R expressing cortical interneuron subtypes revealed by single-cell RNA sequencing.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 2756 Downloadable Samples
- Illumina HiSeq 2500
Description
During cortical development, distinct subtypes of glutamatergic neurons are sequentially born and differentiate from dynamic populations of progenitors. How progenitors and their daughter cells are temporally patterned remains unknown. Here, we trace the transcriptional trajectories of successive generations of apical progenitors (APs) and isochronic cohorts of their daughter neurons in the developing mouse neocortex using high temporal resolution parallel single-cell RNA sequencing. We identify and functionally characterize a core set of evolutionarily-conserved temporally patterned genes which drive APs from internally-driven states to more exteroceptive states, revealing a progressively increasing role for extracellular signals as corticogenesis unfolds. These embryonic age-dependent AP molecular states are reflected in their neuronal progeny as successive ground states, onto which essentially conserved early post-mitotic differentiation programs are applied. Thus, temporally unfolding molecular birthmarks present in progenitors act in their post-mitotic progeny as seeds for adult neuronal diversity. Overall design: Investigation of the transcriptional dynamics in time-locked cohorts of cortical cells across embryonic neurogenesis. Flashtag is injected at 4 ages (E12, E13, E14, E15), and cells collected 1H, 24H, 96H after birth (= a total of 12 conditions) and analyzed by single cell transcriptomics.
Publication Title
Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex.
Sample Metadata Fields
Subject
View Samples- Sus scrofa
- 29 Downloadable Samples
Affymetrix Porcine Genome Array (porcine)
Description
The age groups were used to investigate how gene expression differences between the brachial and the femoral artery effect the heterogeneous atherosclerotic disease initiation and progression.
Publication Title
Gene expression differences in healthy brachial and femoral arteries of Rapacz familial hypercholesterolemic swine.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina HiSeq 2000
Description
To provide further insight about the effects of prolonged Ezh2 inhibition in glioblastoma using preclinical mouse models and doxycycline-inducible shRNAs that mimic the effects of a selective EZH2 inhibitor. We demonstrate that prolonged Ezh2-depletion causes a robust switch in cell fate, including significantly enhanced proliferation and DNA damage repair and activation of part of the pluripotency network, resulting in altered tumor cell identity and tumor progression. Overall design: SVZ derived neural stem cells (NSCs) were isolated from 7 days old p53;Ink4a/Arf;Krasv12;LucR compound conditional mice and cultured in NSC specific serum-free medium supplemented with 20ng/ml of both EGF and bFGF (R&D systems). NSCs were grown adhesion-free for the first passages to eliminate non-sphere-forming cells. Next, cells were grown adherent on poly-L-Ornithine and Laminin plates and three times infected with lentiviral CMV-Cre. These floxed, tumorigenic cells are further referred as glioma initiating cells (GICs). Next, GICs were infected with a tet-inducible, doxycycline-responsive short hairpin construct (FH1-tUTG-shEzh2). After FACS sorting for GFP, GICs were injected intracranial in NOD-SCID mice and treated with or without doxycycline in the drinking water
Publication Title
Prolonged Ezh2 Depletion in Glioblastoma Causes a Robust Switch in Cell Fate Resulting in Tumor Progression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 30 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin.
Sample Metadata Fields
Age, Specimen part, Cell line, Treatment, Time
View Samples- Mus musculus
- 30 Downloadable Samples
Illumina HumanWG-6 v3.0 expression beadchip
Description
One major class of anti-cancer drugs targets topoisomerase II to induce DNA double-strand breaks and cell death of fast growing cells. In vitro experiments showed that doxorubicin can induce histone eviction as well as DNA damage, while etoposide can only induce DNA damage. Here, we compare the transcription responses of different tissues to doxorubicin or etoposide treatment in vivo.
Publication Title
Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin.
Sample Metadata Fields
Age, Specimen part, Treatment, Time
View Samples- Drosophila melanogaster
- 35 Downloadable Samples
- Illumina HiSeq 2000
Description
The ability to cope with infection by a parasite is one of the major challenges for any host species and is a major driver of evolution. Parasite pressure differs between habitats. It is thought to be higher in tropical regions compared to temporal ones. We infected Drosophila melanogaster from two tropical (Malaysia and Zimbabwe) and two temperate populations (the Netherlands and North Carolina) with the generalist entomopathogenic fungus Beauveria bassiana to examine if adaptation to local parasite pressures led to differences in resistance. Contrary to previous findings we observed increased survival in temperate populations. This, however, is not due to increased resistance to infection per se, but rather the consequence of a higher general vigor of the temperate populations. We also assessed transcriptional response to infection within these flies eight and 24 hours after infection. Only few genes were induced at the earlier time point, most of which are involved in detoxification. In contrast, we identified more than 4,000 genes that changed their expression state after 24 hours. This response was generally conserved over all populations with only few genes being uniquely regulated in the temperate populations. We furthermore found that the American population was transcriptionally highly diverged from all other populations concerning basal levels of gene expression. This was particularly true for stress and immune response genes, which might be the genetic basis for their elevated vigor. Overall design: mRNA profiles of whole Drosophila melanogaster adult males from an African, American, Asian and European population after infection with Beauveria bassiana. Samples include uninfected controls, 8h after infection and 24h after infection. 3 biological replicates each (2 in the case of American controls).
Publication Title
Survival Rate and Transcriptional Response upon Infection with the Generalist Parasite Beauveria bassiana in a World-Wide Sample of Drosophila melanogaster.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
- AB SOLiD System 2.0 (Homo sapiens), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MicroRNA 4423 is a primate-specific regulator of airway epithelial cell differentiation and lung carcinogenesis.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st), AB SOLiD System 2.0 (Homo sapiens)
Description
Smoking is a significant risk factor for lung cancer, the leading cause of cancer-related deaths worldwide. While microRNAs are regulators of many airway gene-expression changes induced by smoking, their role in modulating changes associated with lung cancer in these cells remains unknown. Here, we use next-generation sequencing of small RNAs in the airway to identify miR-4423 as a novel primate-specific microRNA associated with lung cancer and expressed primarily in mucociliary epithelium. The endogenous expression of miR-4423 increases as bronchial epithelial cells undergo differentiation into mucociliary epithelium in vitro and its overexpression during this process causes an increase in the number of ciliated cells. Furthermore, expression of miR-4423 is reduced in most lung tumors and in cytologically normal epithelium of the mainstem bronchus of smokers with lung cancer. In addition, ectopic expression of miR-4423 in a subset of lung cancer cell lines reduces their anchorage-independent growth and significantly decreases the size of the tumors formed in a mouse xenograft model. Consistent with these phenotypes, overexpression of miR-4423 induces a differentiated-like pattern of airway epithelium gene expression and reverses the expression of many genes that are altered in lung cancer. Together, our results indicate that miR-4423 is a novel regulator of airway epithelium differentiation and that the abrogation of its function contributes to lung carcinogenesis.
Publication Title
MicroRNA 4423 is a primate-specific regulator of airway epithelial cell differentiation and lung carcinogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE18350- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We describe Hi-C, a method that probes the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. We constructed spatial proximity maps of the human genome with Hi-C at a resolution of 1Mb. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes.
Publication Title
Comprehensive mapping of long-range interactions reveals folding principles of the human genome.
Sample Metadata Fields
Cell line
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