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GSE14009
Caenorhabditis elegans
18 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
RNA Pol II accumulates at promoters of growth genes during developmental arrest.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 18 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
When C. elegans larvae hatch in the absence of food they persist in a stress resistant, developmentally arrested state (L1 arrest). We characterized mRNA expression genome-wide in a pair of bifurcating time series starting in the late embryo and proceeding through the hatch in the presence and absence of food (E. coli).
Publication Title
RNA Pol II accumulates at promoters of growth genes during developmental arrest.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 43 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive weakness from loss of motor neurons. The fundamental pathogenic mechanisms are unknown and recent evidence is implicating a significant role for abnormal exon splicing and RNA processing. Using new comprehensive genomic technologies, we studied exon splicing directly in 12 sporadic ALS and 10 control lumbar spinal cords acquired by a rapid autopsy system that processed nervous systems specifically for genomic studies. ALS patients had rostral onset and caudally advancing disease and abundant residual motor neurons in this region. We created two RNA pools, one from motor neurons collected by laser capture microdissection and one from the surrounding anterior horns. From each, we isolated RNA, amplified mRNA, profiled whole-genome exon splicing, and applied advanced bioinformatics. We employed rigorous quality control measures at all steps and validated findings by qPCR. In the motor neuron enriched mRNA pool, we found two distinct cohorts of mRNA signals, most of which were up-regulated: 148 differentially expressed genes (p103) and 411 aberrantly spliced genes (p105). The aberrantly spliced genes were highly enriched in cell adhesion (p1057), especially cell-matrix as opposed to cell-cell adhesion. Most of the enriching genes encode transmembrane or secreted as opposed to nuclear or cytoplasmic proteins. The differentially expressed genes were not biologically enriched. In the anterior horn enriched mRNA pool, we could not clearly identify mRNA signals or biological enrichment. These findings, perturbed and up-regulated cell-matrix adhesion, suggest possible mechanisms for the contiguously progressive nature of motor neuron degeneration.
Publication Title
Sporadic ALS has compartment-specific aberrant exon splicing and altered cell-matrix adhesion biology.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 138 Downloadable Samples
Description
Multiple myeloma (MM) is a malignant plasma cell disorder with well-defined clonal genetic/cytogenetic abnormalities. However, cellular heterogeneity is a key factor in MM's progression, therapeutic decision, and response to treatment. Single cell whole transcriptome profiling (scRNA-Seq) offers an opportunity to dissect this molecular heterogeneity during MM progression to better understand the disease and guide rational therapy. Here, we examined 597 CD138 positive cells from 15 patients at different stages of MM progression using scRNA-Seq. We selected 790 genes based on a Coefficient of Variation (CV) approach which organized cells into four clusters (L1-L4) based on unsupervised clustering. Plasma cells from each patient contained a mixed population of plasma cells at different state of aggressiveness based on gene expression signature reflecting the inter-cellular heterogeneous nature of MM. Cells in the L1 group is characterized by low level expression of genes involved in the oxidative phosphorylation, Myc targets, and mTORC1 signaling pathway having most cells from MGUS patients (p < 1.2x10-14). In contrast, low level of these genes in L1 group increased progressively and were the highest in the L4 group containing only cells from high-risk MM patients with t(4;14) translocations. Furthermore, 44 genes consistently overexpressed by pair-wised comparisons of the four groups strongly associated with a reduced overall survival in MM patients (APEX trial, p < 0.0001; Hazard Ratio (HR), 1.83; 95% CI, 1.33 to 2.52), particularly those in the bortezomib treated group (p < 0.0001; HR, 2.00; 95% CI, 1.39 to 2.89). No survival significance was observed for the dexamethasone treated group. Our study at the resolution of single cells showed that there is a mixed population of cells in each patient at different stages of MM progression and these cells can be organized into four different subgroups (L1 to L4). Consistent overexpression of the 44 genes from L1 to L4 groups is associated with patient outcome and treatment response. Our results show that oxidative phosphorylation, Myc target, and mTORC1 signaling genes are significant pathways for MM progression and affect MM prognosis and treatment stratification. Overall design: 597 single cell libraries passed QC and were included in the downstream analysis
Publication Title
Molecular signatures of multiple myeloma progression through single cell RNA-Seq.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 10 Downloadable Samples
- NextSeq 500
Description
We profiled how animals RNA expression changes in response to osmotic stress, how lin-45 mutants have an altered response to osmotic stress, and how maternal preconditioning at 300 mM NaCl modifies progeny response to 500 mM NaCl Overall design: Examination of total RNAseq at 50 mM NaCl, 500 mM NaCl, and 500 mM NaCl from maternally preconditioned animals
Publication Title
Insulin-like signalling to the maternal germline controls progeny response to osmotic stress.
Sample Metadata Fields
Subject, Time
View Samples- Mus musculus, Homo sapiens
- 44 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Profiling bortezomib resistance identifies secondary therapies in a mouse myeloma model.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Genome-wide analysis of gene expression in response to bortezomib treatment (33 nM) in cell lines before and after selection for resistance.
Publication Title
Profiling bortezomib resistance identifies secondary therapies in a mouse myeloma model.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Genome-wide analysis of gene expression in response to bortezomib treatment(33 nM) in cell lines before and after selection for resistance.
Publication Title
Profiling bortezomib resistance identifies secondary therapies in a mouse myeloma model.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Caenorhabditis elegans
- 123 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
This series of samples comprises multiple early embryonic time courses for C. elegans. Time courses consisting of 10 time points each for 4 different genotypes are included: wild-type (strain N2 grown on E. coli strain OP50), pie-1(zu154) (progeny of homozygous mutant mothers [Unc] of strain JJ532 grown on E. coli strain OP50), pie-1(zu154);pal-1(RNAi) (progeny of homozygous mutant mothers [Unc] of strain JJ532 grown on E. coli strain HT115 expressing pal-1 hairpin RNA), and mex-3(zu155);skn-1(RNAi) (progeny of homozygous mutant mothers [Dpy] of strain JJ518 grown on E. coli strain HT115 expressing skn-1 hairpin RNA). Embryos were manually staged by morphology at the 4-cell stage and allowed to develop in water for defined amounts of time at 22 degrees C. RNA was amplified as described (Baugh et al. Development, 2003; Baugh et al. Nucleic Acids Research, 2001). This series of samples comprises all replicate data reported by Baugh et al. (Development, 2005).
Publication Title
The homeodomain protein PAL-1 specifies a lineage-specific regulatory network in the C. elegans embryo.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 74 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Biological networks are inherently modular, yet little is known about how modules are assembled to enable coordinated and complex functions. We used RNAi and time-series, whole-genome microarray analyses to systematically perturb and characterize components of a C. elegans lineage-specific transcriptional regulatory network. These data are supported by select reporter gene analyses and comprehensive yeast-one-hybrid and promoter sequence analyses. Based on these results we define and characterize two modules composed of muscle- and epidermal-specifying transcription factors that function together within a single cell lineage to robustly specify multiple cell types. The expression of these two modules, although positively regulated by a common factor, is reliably segregated among daughter cells. Our analyses indicate that these modules repress each other, and we propose that this cross-inhibition coupled with their relative time of induction function to enhance the initial asymmetry in their expression patterns, thus leading to the observed invariant gene expression patterns and cell lineage. The coupling of asynchronous and topologically distinct modules may be a general principle of module assembly that functions to potentiate genetic switches.
Publication Title
Pairing of competitive and topologically distinct regulatory modules enhances patterned gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples