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SRP082327
Mus musculus
924 Downloadable Samples
NextSeq 500
Description
We report RNA-seq of single nuclei isolated from the adult C57BL/6 male mouse Hippocampus region. Majority of the nuclei were isolated from 12 weeks old mice (4 different animal), with an additional set of nuclei from 3 months and 2 years old animals. In addition a set of GFP labeled nuclei driven by a VGAT promoter . Overall design: Microdissections of dentate gyrus, CA1 and CA2/3 regions of the Hippocampus were placed into ice-cold RNA-later for fixation and stored at 4°c overnight, then stored in -80°c. Nuclei were isolated by sucrose gradient centrifugation and kept on ice until sorting using Fluorescence Activated Cell Sorting (FACS) into 96 well plates containing RNA lysis buffer. Single nucleus RNA was first purified then derived cDNA libraries were generated following a modified Smart-seq2 protocol. For VGAT nuclei: high titer AAV1/2 of pAAV-EF1a-DIO-EYFP-KASH-WPRE-hGH-polyA was injected into dorsal and/or ventral Hippocampus, animals were sacrificed two weeks after injections, and GFP labeled nuclei were sorted into plates and processed as described above.
Publication Title
Div-Seq: Single-nucleus RNA-Seq reveals dynamics of rare adult newborn neurons.
Sample Metadata Fields
Age, Cell line, Subject
View Samples- Homo sapiens
- 20 Downloadable Samples
- Illumina HiSeq 2500
Description
RUNX1 is a frequent target of translocations in acute myeloid leukemia whereby its DNA binding domain fuses to different epigenetic regulators. To assess how different RUNX1 fusion proteins interact with the epigenome we compared the global binding patterns and the chromatin landscape of t(8;21) and t(3;21) AML which express RUNX1-ETO and RUNX1-EVI-1, respectively. We found that differential prognosis for these types of AML is reflected in fundamental differences in gene expression, chromatin landscape, binding patterns of the fusion proteins and other transcription factors as identified by genome-wide digital footprinting in patients. As previously shown for RUNX1-ETO, knockdown of RUNX1-EVI-1 expression initiates differentiation of t(3;21) cells which is associated with up-regulation of genes vital for myeloid differentiation, including C/EBPa. Furthermore, by expressing either dominant-negative C/EBP or an inducible C/EBPa construct in t(3;21) cells we show that C/EBPa is necessary and sufficient for the differentiation response of these cells to RUNX1-EVI-1 knockdown. Overall design: RNA-seq expreiments have been used to study the chromatin landscape of t(8;21) and t(3;21) AML
Publication Title
RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 28 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We demonstrate the in vivo efficacy of the histone deacetylase inhibitor Panobinostat (LHB589) against MLL-rearranged ALL using xenograft mouse models of MLL-rearranged ALL cell lines and primary patient cells. Panobinostat monotherapy showed strong anti-leukaemic effects, extending survival and reducing overall disease burden. Comprehensive molecular analyses in vitro showed the anti-leukaemic activity in MLL-rearranged ALL to involve depletion of H2B ubiquitination via suppression of the RNF20/RNF40/WAC E3 ligase complex.
Publication Title
The HDAC inhibitor panobinostat (LBH589) exerts in vivo anti-leukaemic activity against MLL-rearranged acute lymphoblastic leukaemia and involves the RNF20/RNF40/WAC-H2B ubiquitination axis.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Circadian clocks are cell-autonomous oscillators regulating daily rhythms in a wide range of physiological, metabolic and behavioral processes. Conversely, metabolic signals such as redox state, NAD+/NADH and AMP/ADP ratios or heme feed back to and modulate circadian mechanisms to optimize energy utilization across the 24-hour cycle. We show that the signaling molecule carbon monoxide (CO) generated by rhythmic heme degradation is required for normal circadian rhythms as well as circadian metabolic outputs.
Publication Title
Reciprocal regulation of carbon monoxide metabolism and the circadian clock.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Retinol Saturase (RetSat) is an oxidoreductase expressed at high levels in the hepatocyte fraction of liver.
Publication Title
Retinol saturase coordinates liver metabolism by regulating ChREBP activity.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 24 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Exposure to environmental contaminants can disrupt normal development of the early vertebrate skeleton. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) impairs craniofacial skeletal development across many vertebrate species and its effects are especially prominent in early life stages of fish. TCDD activates the aryl hydrocarbon receptor (AHR), a transcription factor that mediates most if not all TCDD responses. We investigated the transcriptional response in the developing zebrafish jaw following TCDD exposure using DNA microarrays. Zebrafish larvae were exposed to TCDD at 96 h postfertilization (hpf) and jaw cartilage tissue was harvested for microarray analysis at 1, 2, 4 and 12 h postexposure (hpe). Numerous chondrogenic transcripts were misregulated by TCDD in the jaw. Comparison of transcripts altered by TCDD in jaw with transcripts altered in embryonic heart showed that the transcriptional responses in the jaw and the heart were strikingly different. Sox9b, a critical chondrogenic transcription factor, was the most significantly reduced transcript in the jaw. We hypothesized that the TCDD reduction of sox9b expression plays an integral role in affecting formation of the embryonic jaw. Morpholino knock down of sox9b expression demonstrated that partial reduction of sox9b expression alone was sufficient to produce a TCDD-like jaw phenotype. Heterozygous sox9b deletion mutant embryos were sensitized to TCDD. Lastly, embryos injected with sox9b mRNA and then exposed to TCDD blocked TCDD-induced jaw toxicity in approximately 14% of sox9b-injected embryos. These results suggest that reduced sox9b expression in TCDD-exposed zebrafish embryos contributes to jaw malformation.
Publication Title
Aryl hydrocarbon receptor-mediated down-regulation of sox9b causes jaw malformation in zebrafish embryos.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 8 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Microarrays were conducted to asses the effect of Stb3 deletion in immediate transcriptional induction in response to glucose
Publication Title
Stb3 binds to ribosomal RNA processing element motifs that control transcriptional responses to growth in Saccharomyces cerevisiae.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 8 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
2,3,7,8-TCDD (TCDD) is a reproductive toxicant and endocrine disruptor in nearly all vertebrates, yet the mechanisms by which TCDD induces these reproductive alterations have not been fully characterized. Fish are among the most sensitive vertebrates to the toxic effects of TCDD, and even subtle physiologic changes induced by TCDD can impair reproduction. Previously, we have shown that chronic, sub-lethal exposure to TCDD decreased reproductive capacity, reduced serum estradiol and vitellogenin concentrations, and altered follicular development. Here we investigate the transcriptional changes in zebrafish ovary as they relate to observed attenuated estradiol concentrations and ovarian development. We used quantitative RT-PCR to assess TCDDs effects on the expression of several candidate genes important in the regulation of follicular development and steroidogenesis. Additionally, global changes in gene expression in the ovary caused by TCDD exposure were identified using Affymetrix Gene Chip Analysis. Our data suggest that TCDD may inhibit follicle maturation via attenuated gonadotropin responsiveness and/or depressed estradiol biosynthesis. Additionally, genes involved in glucose and lipid metabolism, regulation of transcription, and immune function were dysregulated by at least 2-fold suggesting that TCDD alters various integrated networks of signaling pathways. Approximately 89% of dysregulated transcripts contain putative AHR response elements (AHRE) within 5kb upstream of the predicted transcriptional start site suggesting ovarian toxicity is AHRE driven. Furthermore, approximately 49% of dysregulated transcripts contain putative estrogen response elements (ERE) suggesting that dysregulation of estrogen-responsive genes may also contribute to TCDD-induced attenuated follicular development. Patterns in gene expression were correlated with putative EREs and AHREs, and suggest that impacts on the regulation of transcription may play a large role in TCDDs ovarian toxicity. Taken together, these data illustrate the complexity of TCDDs ovarian toxicity.
Publication Title
Molecular targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) within the zebrafish ovary: insights into TCDD-induced endocrine disruption and reproductive toxicity.
Sample Metadata Fields
Sex, Specimen part
View Samples- Danio rerio
- 48 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Retinoic acid (RA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin activate distinct ligand-dependent transcription factors, and both cause cardiac malformation and heart failure in zebrafish embryos. We hypothesized that they cause this response by hyperactivating a common set of genes critical for heart development. To test this, we used microarrays to measure transcripts changes in hearts isolated from zebrafish embryos 1,2,4 and 12 h after exposure to 1M RA. We used hierarchical clustering to compare the transcriptional responses produced in the embryonic heart by RA and TCDD. We could identify no early responses in common between the two agents. However, at 12 h both treatments produced a dramatic downregulation of a common cluster of cell cycle progression genes, which we term the Cell Cycle Gene Cluster (CCGC). This was associated with a halt in heart growth. These results suggest that RA and TCDD ultimately trigger a common transcriptional response associated with heart failure, but not through the direct activation of a common set of genes. Among the genes rapidly induced by RA was Nr2F5, a member of the COUP-TF family of transcription repressors. We found that induction of Nr2F5 was both necessary and sufficient for the cardiotoxic response to RA.
Publication Title
Comparative genomics identifies genes mediating cardiotoxicity in the embryonic zebrafish heart.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 12 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
The purpose of this experiment is to understand which transcripts are differentially expressed following exposure to TCDD.
Publication Title
TCDD inhibits heart regeneration in adult zebrafish.
Sample Metadata Fields
Treatment
View Samples