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GSE67999
Homo sapiens
12 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Alveolar rhabdomyosarcoma (aRMS) is a soft tissue sarcoma associated with the skeletal muscle lineage. The majority of aRMS tumors express the fusion protein PAX3-FOXO1 (PF), which has proven chemically intractable. As such, we identified proteins downstream from or cooperate with PF to support tumorigenesis, including SFRP3 (FRZB). Suppression of SFRP3 using lentivirally transduced shRNAs inhibits cell growth in vitro and tumor growth in vivo. This study aims to identify the genetic changes that underlie the SFRP3 suppression-mediated decreased cell growth. We analyzed changes using Gene Ontology (GO) enrichment and found the induced genes were enriched in striated muscle development/differentiation. In contrast, the repressed genes were enriched in response to stimulus and cell cycle/mitosis genes. We also observed as expected downregulation of SFRP3 (FRZB) but also downregulation of Wnt pathway-repressing genes such as CTBP2 (a transcriptional repressor of TCF, similar to CTBP1 ) and NAV2 (which is downstream from APC). Conversely, we noted upregulation of genes including CCND1 (cyclin D1) and SNAI2 (SLUG), both Wnt signaling target genes and WNT6, which is known to inhibit myoblast proliferation but induce myoblast elongation.
Publication Title
Secreted Frizzled-Related Protein 3 (SFRP3) Is Required for Tumorigenesis of PAX3-FOXO1-Positive Alveolar Rhabdomyosarcoma.
Sample Metadata Fields
Disease, Cell line, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Alveolar rhabdomyosarcoma (aRMS) is an aggressive sarcoma of skeletal muscle characterized by expression of the PAX3-FOXO1 fusion gene. Despite its discovery over almost 20 years ago, PAX3-FOXO1 remains an enigmatic tumor driver. Previously, we reported that PAX3-FOXO1 supports aRMS initiation by enabling bypass of cellular senescence. Here, we show that bypass occurs in part by PAX3-FOXO1-mediated upregulation of RASSF4, a Ras-association domain family (RASSF) member, which then suppresses the evolutionarily conserved mammalian Hippo/Mst1 pathway. RASSF4 loss-of-function activates Hippo/Mst1 and inhibits downstream YAP, causing aRMS cell cycle arrest and senescence. This is the first evidence for an oncogenic role for RASSF4, and a novel mechanism for Hippo signaling suppression in human cancer.
Publication Title
Alveolar rhabdomyosarcoma-associated PAX3-FOXO1 promotes tumorigenesis via Hippo pathway suppression.
Sample Metadata Fields
Cell line, Treatment
View Samples- Danio rerio
- 6 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Fluorescent-labeled zebrafish RAS-induced embryonal rhabdomyosarcoma (ERMS) were created to facilitate in vivo imaging of tumor-propagating cells, regional tumor heterogeneity, and dynamic cell movements in diverse cellular compartments. Using this strategy, we have identified a molecularly distinct ERMS cell subpopulation that expresses high levels of myf5 and is enriched for ERMS-propagating potential when compared with other tumor-derived cells.
Publication Title
In vivo imaging of tumor-propagating cells, regional tumor heterogeneity, and dynamic cell movements in embryonal rhabdomyosarcoma.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina HiSeq 2000
Description
PTBP1 and PTBP2 control alternative splicing programs during neuronal development, but the cellular functions of most PTBP1/2-regulated isoforms remain unknown. We show that PTBP1 guides developmental gene expression by regulating the transcription factor Pbx1. We identify exons that are differentially spliced when mouse embryonic stem cells (ESCs) differentiate into neuronal progenitor cells (NPCs) and neurons, and transition from PTBP1 to PTBP2 expression. We define those exons controlled by PTBP1 in ESCs and NPCs by RNA-seq analysis after PTBP1 depletion and PTBP1 crosslinking-immunoprecipitation. We find that PTBP1 represses Pbx1 exon 7 and the expression of its neuronal isoform Pbx1a in ESC. Using CRISPR-Cas9 to delete regulatory elements for exon 7, we induce Pbx1a expression in ESCs, finding that this activates transcription of specific neuronal genes including known Pbx1 targets. Thus PTBP1 controls the activity of Pbx1 and suppresses its neuronal transcriptional program prior to differentiation. Overall design: 46C mESCs were differentiated in mNPCs. The mNPCs were treated with 10 nM control, Ptbp1, Ptbp2, or Ptbp1 and Ptbp2 siRNAs for 48 hours. The knockdowns were performed using 2 independent sets of siRNAs. Poly-A RNA was isolated for RNA-sequencing and splicing analyses.
Publication Title
The splicing regulator PTBP1 controls the activity of the transcription factor Pbx1 during neuronal differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 27 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The cell of origin for rhabdomyosarcoma (RMS) and undifferentiated pleomorphic sarcoma (UPS) remains to be determined. We utilized two skeletal muscle specific inducible Cre mouse lines to transform both skeletal muscle stem cells and progenitors to determine which cells give rise to RMS and UPS.
Publication Title
Distinct and overlapping sarcoma subtypes initiated from muscle stem and progenitor cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Murine Pulmonary Responses to Ambient Baltimore Particulate Matter: Genomic Analysis and Contribution to Airway Hyperresponsiveness
Publication Title
Murine lung responses to ambient particulate matter: genomic analysis and influence on airway hyperresponsiveness.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 39 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Purpose: To investigate the gene regulatory networks during photoreceptor differentiation.
Publication Title
Targeting of GFP to newborn rods by Nrl promoter and temporal expression profiling of flow-sorted photoreceptors.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The presence of some malignancies, such as cancer, impacts on peripheral blood mononuclear cells (PBMCs) gene expression profiling, suggesting the potential suitability of these genes as diagnostic and prognostic markers.
Publication Title
Transcriptional profiling of peripheral blood in pancreatic adenocarcinoma patients identifies diagnostic biomarkers.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Particulate Matter Triggers Carotid Body Dysfunction, Respiratory Dysynchrony and Cardiac Arrhythmias in Mice with Cardiac Failure
Publication Title
Particulate matter induces cardiac arrhythmias via dysregulation of carotid body sensitivity and cardiac sodium channels.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 251 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
593 FFPE colorectal cancer samples were used to generate three prediction models: Recurrence prediction, 5FU efficacy prediction, and FOLFOX efficacy prediction
Publication Title
Building personalized treatment plans for early-stage colorectal cancer patients.
Sample Metadata Fields
Specimen part
View Samples