Filters
Technology
Platform
GSE144829
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Different osteoprogenitors (SSC, BCSP, Thy+) were sorted after 2 days of JUN induction, followed by RNA extraction and microarray analysis
Publication Title
Expansion of Bone Precursors through Jun as a Novel Treatment for Osteoporosis-Associated Fractures.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Time course analysis of c-Jun expression at 24h resulted in upregulation of a number of well-known fibrogenesis-associated factors.
Publication Title
Unifying mechanism for different fibrotic diseases.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In mammals, sex differentiation of primordial germ cells (PGCs) is determined by extrinsic cues from the environment1. In female PGCs, expression of Stimulated by retinoic acid 8 (Stra8) and meiosis are induced in response to retinoic acid (RA) provided by the mesonephroi2-4. Given the widespread role of RA signaling during development8,9, the molecular mechanism specifying the competence of PGCs to timely express Stra8 and enter meiosis are unknown2,10. Here we identify gene dosage dependent roles in PGC development for Ring1 and Rnf2, two central components of the Polycomb Repressive Complex 1 (PRC1)11,13. Both paralogs are essential for PGC development between day 10.5 and 11.5 of gestation. Rnf2 is subsequently required in female PGCs for maintaining high levels of Oct4 and Nanog expression6, and for preventing premature induction of meiotic gene expression and entry into meiotic prophase. Chemical inhibition of RA signaling partially suppresses precocious Oct4 down-regulation and Stra8 activation in Rnf2-deficient female PGCs. Chromatin immunoprecipitation analyses show that Stra8 is a direct target of PRC1 and PRC2 in PGCs. These data demonstrate the importance of PRC1 gene dosage in PGC development and in coordinating the timing of sex differentiation of female PGCs by antagonizing extrinsic RA signaling.
Publication Title
PRC1 coordinates timing of sexual differentiation of female primordial germ cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
In mammals, sex differentiation of primordial germ cells (PGCs) is determined by extrinsic cues from the environment1. In female PGCs, expression of Stimulated by retinoic acid 8 (Stra8) and meiosis are induced in response to retinoic acid (RA) provided by the mesonephroi2-4. Given the widespread role of RA signaling during development8,9, the molecular mechanism specifying the competence of PGCs to timely express Stra8 and enter meiosis are unknown2,10. Here we identify gene dosage dependent roles in PGC development for Ring1 and Rnf2, two central components of the Polycomb Repressive Complex 1 (PRC1)11,13. Both paralogs are essential for PGC development between day 10.5 and 11.5 of gestation. Rnf2 is subsequently required in female PGCs for maintaining high levels of Oct4 and Nanog expression6, and for preventing premature induction of meiotic gene expression and entry into meiotic prophase. Chemical inhibition of RA signaling partially suppresses precocious Oct4 down-regulation and Stra8 activation in Rnf2-deficient female PGCs. Chromatin immunoprecipitation analyses show that Stra8 is a direct target of PRC1 and PRC2 in PGCs. These data demonstrate the importance of PRC1 gene dosage in PGC development and in coordinating the timing of sex differentiation of female PGCs by antagonizing extrinsic RA signaling. Overall design: Gene expression of mouse primordial germ cells was analysed using RNAseq method. Primodial germ cells were purified from embryos carrying Oct4(-delta-PE)-GFP transgene by FACS.
Publication Title
PRC1 coordinates timing of sexual differentiation of female primordial germ cells.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 161 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A NOTCH3 transcriptional module induces cell motility in neuroblastoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Migratory embryonal neuroblasts give rise to several tissues, including the sympathetic nervous system (SNS). Neuroblastomas are paediatric tumours of the peripheral SNS with a highly variable prognosis. We observed that high NOTCH3 expression in neuroblastomas correlated with a poor prognosis. Expression of a NOTCH3 transgene in neuroblastoma cells induced many motility genes and conferred a highly motile phenotype. Expression of these motility genes strongly correlated with NOTCH3 expression in neuroblastomas and many other tumours, suggesting a general role for NOTCH3 in regulation of these genes. Silencing of NOTCH3 or genes of the Notch-processing -secretase complex induced apoptosis in all neuroblastoma cell lines tested. These data suggest that NOTCH3 is a key-regulator of motility, and indispensable for survival of neuroblastoma cells.
Publication Title
A NOTCH3 transcriptional module induces cell motility in neuroblastoma.
Sample Metadata Fields
Cell line
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- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Neuroblastoma is a pediatric tumor of the sympathetic nervous system. MYCN (V-myc myelocytomatosis viral-related oncogene, neuroblastoma derived [avian]) is amplified in 20% of neuroblastomas, and these tumors carry a poor prognosis. However, tumors without MYCN amplification also may have a poor outcome. Here, we identified downstream targets of MYCN by shRNA-mediated silencing MYCN in neuroblastoma cells. From these targets, 157 genes showed an expression profile correlating with MYCN mRNA levels in NB88, a series of 88 neuroblastoma tumors, and therefore represent in vivo relevant MYCN pathway genes. This 157-gene signature identified very poor prognosis tumors in NB88 and independent neuroblastoma cohorts and was more powerful than MYCN amplification or MYCN expression alone. Remarkably, this signature also identified poor outcome of a group of tumors without MYCN amplification. Most of these tumors have low MYCN mRNA levels but high nuclear MYCN protein levels, suggesting stabilization of MYCN at the protein level. One tumor has an MYC amplification and high MYC expression. Chip-on-chip analyses showed that most genes in this signature are directly regulated by MYCN. MYCN induces genes functioning in cell cycle and DNA repair while repressing neuronal differentiation genes. The functional MYCN-157 signature recognizes classical neuroblastoma with MYCN amplification, as well as a newly identified group marked by MYCN protein stabilization.
Publication Title
Functional MYCN signature predicts outcome of neuroblastoma irrespective of MYCN amplification.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A NOTCH feed-forward loop drives reprogramming from adrenergic to mesenchymal state in neuroblastoma.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Homo sapiens
- 86 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
mRNA profiles of thousands of human tumors are available, but methods to deduce oncogenic signaling networks from these data lag behind. It is especially challenging to identify main-regulatory routes, and to generalize conclusions obtained from experimental models. We designed the bioinformatic platform R2 in parallel with a wet-lab approach of neuroblastoma. Here we demonstrate how R2 facilitates an integrated analysis of our neuroblastoma data. Analysis of the MYCN pathway suggested important regulatory connections to the polyamine synthesis route, the Notch pathway and the BMP/TGF pathway. A network of genes emerged connecting major oncogenes in neuroblastoma. Genes in the network carried strong prognostic values and were essential for tumor cell survival.
Publication Title
Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes.
Sample Metadata Fields
Specimen part
View Samples