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SRP131871
Homo sapiens
4 Downloadable Samples
Description
How genomic information is selectively utilized to direct spatial and temporal gene expression patterns during differentiation remains to be elucidated but it is clear that regulated changes in higher-order genomic architecture plays a fundamental role. Specifically, long range interactions within and between chromosomes and the position of chromosome territories in the nucleus are controlled by TADs and LADs respectively, but the relationship between these genomic organizers remains poorly understood Overall design: We analyzed the large-scale spatial reorganization of chromatin by generating matched Hi-C and nuclear lamin-chromatin contact datasets throughout a dual adipose/neuronal induction of human primary adipose stem cells. We have mapped Hi-C (TADs) and lamin-associated domains (LADs) in multiple steps during adipose stem cell differentiation to characterize the spatial and temporal link between genomic architecture and gene expression. We identify a new level of 4D genomic organization involving a long-range clustering of individual TADs or TAD pairs into TAD cliques. LADs appear to regulate their formation. (ASCs). We unveil a lineage-specific dynamic assembly and disassembly of repressive cliques of linearly non-contiguous TADs, and a time course-coupled relationship between TAD clique size and lamina association. Our findings reveal a new level of developmental genome organization and provide an overview of large-scale changes in the 4D nucleome during lineage-specific differentiation.
Publication Title
Long-range interactions between topologically associating domains shape the four-dimensional genome during differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 40 Downloadable Samples
- Illumina Genome Analyzer II
Description
Background: West Nile virus is an emerging infection of biodefense concern and there are no available treatments or vaccines. Here we used a high-throughput method based on a novel gene expression analysis, RNA-Seq, to give a global picture of differential gene expression by primary human macrophages of 10 healthy donors infected in vitro with WNV. Results: From a total of 50 million reads per sample, we employed a Bayesian hierarchical mixture model to identify 4,026 transcripts that were differentially expressed after infection. Both predicted and novel gene changes were detected, as were gene isoforms, and while many of the genes were expressed by all donors, some were unique. Knock-down of genes not previously known to be associated with WNV resistance identified their critical role in control of viral infection. Conclusions: Our study distinguishes both common gene pathways as well as novel cellular responses. Such analysis will be valuable for translational studies of susceptible and resistant individuals -- and for targeting therapeutics -- in multiple biological settings. Overall design: Differential gene expression by primary human macrophages of 10 healthy donors infected in vitro with WNV were generated by RNA-Seq.
Publication Title
Identification of genes critical for resistance to infection by West Nile virus using RNA-Seq analysis.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
IL-17-producing CD8+ (Tc17)T cells are implicated in the pathogenesis of multiple sclerosis (MS), thereby representing a promising target for therapy. We found that dimethyl fumarate (DMF), a first-line medication for MS upregulated reactive oxygen species (ROS) by glutathione depletion in murine Tc17 cells, which limited IL-17 and diverted Tc17 cells towards cytotoxic T lymphocyte (CTL) signature. DMF enhanced PI3K-AKT-FOXO1-T-bet- as well as STAT5-signaling leading to restricted permissive histone state at the Il17 locus. T-bet-deficiency, inhibiting PI3K-AKT, STAT5 or histone deacetylases prevented DMF-ROS-mediated IL-17 suppression. In MS patients with stable response, DMF suppressed IL-17 production by CD8+ T-cells and triggered diversion from Tc17 towards CTL signature along with enriched ROS-, PI3K-AKT-FOXO1-signaling, demonstrating comparable regulation across species. Accordingly, in the mouse model for MS, DMF limited Tc17-encephalitogenicity. Our findings disclose DMF-ROS-AKT-driven pathway, which selectively modulates Tc17 fate to ameliorate MS, thus opening avenue to develop markers and targets for specific therapy. Overall design: Examination of DMF-induced expression changes in 3 conditions, 3 samples each: murine TC17 cells without treatment as control group, murine Tc17 cells treated with DMF and murine Tc17 cells treated with DMF and Glutathione(GSH)
Publication Title
IL-17<sup>+</sup> CD8<sup>+</sup> T cell suppression by dimethyl fumarate associates with clinical response in multiple sclerosis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
IL-17-producing CD8+ (Tc17)T cells are implicated in the pathogenesis of multiple sclerosis (MS), thereby representing a promising target for therapy. We found that dimethyl fumarate (DMF), a first-line medication for MS upregulated reactive oxygen species (ROS) by glutathione depletion in murine Tc17 cells, which limited IL-17 and diverted Tc17 cells towards cytotoxic T lymphocyte (CTL) signature. DMF enhanced PI3K-AKT-FOXO1-T-bet- as well as STAT5-signaling leading to restricted permissive histone state at the Il17 locus. T-bet-deficiency, inhibiting PI3K-AKT, STAT5 or histone deacetylases prevented DMF-ROS-mediated IL-17 suppression. In MS patients with stable response, DMF suppressed IL-17 production by CD8+ T-cells and triggered diversion from Tc17 towards CTL signature along with enriched ROS-, PI3K-AKT-FOXO1-signaling, demonstrating comparable regulation across species. Accordingly, in the mouse model for MS, DMF limited Tc17-encephalitogenicity. Our findings disclose DMF-ROS-AKT-driven pathway, which selectively modulates Tc17 fate to ameliorate MS, thus opening avenue to develop markers and targets for specific therapy. Overall design: CD8+ memory cells from human blood
Publication Title
IL-17<sup>+</sup> CD8<sup>+</sup> T cell suppression by dimethyl fumarate associates with clinical response in multiple sclerosis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
RhoB null mice show decreases in pathological angiogenesis in the ischemic retina and reduces angiogenesis in response to cutaneous wounding, but enhances lymphangiogenesis following both dermal wounding and inflammatory challenge.
Publication Title
RhoB controls coordination of adult angiogenesis and lymphangiogenesis following injury by regulating VEZF1-mediated transcription.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To clarify mineralcorticoid receptor and glucocorticoid receptor-dependent gene networks in decidualizing human endometrial stromal cells.
Publication Title
Induction of 11β-HSD 1 and activation of distinct mineralocorticoid receptor- and glucocorticoid receptor-dependent gene networks in decidualizing human endometrial stromal cells.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We established a novel EGFP reporter mouse line (named Tg(ETAR-EGFP)14Imeg), which enables the placode-derived inner ear sensory cell lineage to be visualized and monitored. At E10.5, EGFP expression was detected in the ventral and dorsomedial region of the otocyst.
Publication Title
Establishment of mice expressing EGFP in the placode-derived inner ear sensory cell lineage and FACS-array analysis focused on the regional specificity of the otocyst.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Huntingtons disease (HD) is a dominantly inherited genetic disease caused by mutant huntingtin (htt) protein with expanded polyglutamine tracts. A neuropathological hallmark of HD is the presence of neuronal inclusions of mutant htt. p62 is an important regulatory protein in selective autophagy, a process by which aggregated proteins are degraded, and it is associated with several neurodegenerative disorders including HD. Here we investigated the effect of p62 depletion in three HD model mice: R6/2, HD190QG and HD120QG mice. We found that loss of p62 in these models led to longer lifespans and reduced nuclear inclusions, although cytoplasmic inclusions increased with polyglutamine length. In mouse embryonic fibroblasts (MEFs) with or without p62, mutant htt with a nuclear localization signal (NLS) showed no difference in nuclear inclusion between the two MEF types. In the case of mutant htt without NLS, however, p62 depletion increased cytoplasmic inclusions. Furthermore, to examine the effect of impaired autophagy in HD model mice, we crossed R6/2 mice with Atg5 conditional knockout mice. These mice also showed decreased nuclear inclusions and increased cytoplasmic inclusions, similar to HD mice lacking p62. These data suggest that the genetic ablation of p62 in HD model mice enhances cytoplasmic inclusion formation by interrupting autophagic clearance of polyQ inclusions. This reduces polyQ nuclear influx and paradoxically ameliorates disease phenotypes by decreasing toxic nuclear inclusions.
Publication Title
Depletion of p62 reduces nuclear inclusions and paradoxically ameliorates disease phenotypes in Huntington's model mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The onset of the liver inflamentation in the Sox17+/- embryos.
Publication Title
Sox17 haploinsufficiency results in perinatal biliary atresia and hepatitis in C57BL/6 background mice.
Sample Metadata Fields
Specimen part
View Samples- Gallus gallus, Mus musculus, Xenopus laevis
- 80 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
One of the central issues in evolutionary developmental biology is how we can formulate the relationships between evolutionary and developmental processes. Two major models have been proposed: the 'funnel-like' model, in which the earliest embryo shows the most conserved morphological pattern, followed by diversifying later stages, and the 'hourglass' model, in which constraints are imposed to conserve organogenesis stages, which is called the phylotypic period. Here we perform a quantitative comparative transcriptome analysis of several model vertebrate embryos and show that the pharyngula stage is most conserved, whereas earlier and later stages are rather divergent. These results allow us to predict approximate developmental timetables between different species, and indicate that pharyngula embryos have the most conserved gene expression profiles, which may be the source of the basic body plan of vertebrates.
Publication Title
Comparative transcriptome analysis reveals vertebrate phylotypic period during organogenesis.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage
View Samples